FAP inhibitors

ABSTRACT

The present invention concerns compounds, according to general formula (I), which find utility preferably for the treatment of cancer.

FIELD OF THE INVENTION

The present invention relates to compounds, which act as FAP inhibitors,pharmaceutical products comprising the compounds, and methods oftreatment using the compounds.

BACKGROUND

The enzyme fibroblast activation protein alpha (FAPα), hereinabbreviated FAP, is a serine protease that possessesdipeptidyl-peptidase activity specific for N-terminal Xaa-Pro sequences.In addition to the dipeptidyl peptidase activity FAP also possessescollagenolytic activity capable of degrading gelatin and type Icollagen. FAP is a type II transmembrane serine protease which isexpressed as a homodimer. The 95-kDa protein exhibits 48% amino acididentity with DPIV and displays structural similarity to other membersof the dipeptidyl peptidase family including DP8 and DP9. Unlike DPIV,FAP has also been reported to possess endopeptidase activity(Aertgeerts, J. Biol. Chem., 2005, 280, 19441). FAP overexpression hasbeen shown to potentiate tumour growth (Cheng, Mol. Cancer. Ther., 2005,4, 351), and this potentiation is dependent upon its enzymatic activity.Natural substrates for FAP have not yet been identified. FAP is notexpressed by normal mature somatic tissues and benign epithelial tumoursbut is expressed on stromal fibroblasts in more than 90% of carcinomasincluding breast, colon, ovarian, bladder and pancreas (Garin-Chesa etal., Proc. Natl. Acad. Sci., 1990, 87: 7235) as determined byimmunohistochemistry, making this a very specific target for potentialanti-tumour agents. Expression of FAP has also been correlated withinvasive potential of melanoma cells (Aoyama et al., Proc. Natl. Acad.Sci., 1990, 87: 8296) and its presence has been associated withmetastasis of colorectal tumours (Iwasa et al., Cancer Letts., 2003,199: 91). Its presence has been shown to increase tumour formation inanimal models (Cheng et al., Cancer Res., 2002, 62: 4767).

The catalytic action of FAP expressed in stromal fibroblasts incarcinomas has been utilised in the conversion of prodrugs of cytotoxicor cytostatic drugs to active drugs as a potential treatment for cancer(EP 1333033).

In addition to its activity in tumour tissue FAP is also expressed inorgans undergoing non-malignant remodelling, for example liver fibrosis(Levy et al., Hepatol., 1999, 29: 1768). In patients with fibrosis as aresult of alcohol abuse or viral challenge, the cells responsible forthe excessive scarring and constriction of the liver express largequantities of FAP. There is evidence to suggest that FAP plays animportant role in the formation of the fibrotic scar.

Normal tissue is normally FAP negative, however, it is found transientlyin healing wounds (Ramirez-Montagut et al., Oncogene, 2004, 23, 5435)and it is possible FAP plays a role in tissue remodelling and repair.Other potential indications for FAP inhibitors include blood celldisorders such as anemia and chemotherapy-induced neutopenia (Rosenblumet al., Curr. Opin. Chem. Biol., 2003, 7, 496).

The only FAP inhibitor reported to date is ValboroPro (PT-100,Talobostat) which has been reported to show potent anti-tumour activityin mice, slowing growth of syngeneic tumours and causing regression andrejection of tumours after oral administration (Adams et al., CancerRes., 2004, 64: 5471). This compound is currently undergoing clinicaltrials as a treatment for cancer (McIntyre, Drugs of the Future, 2004,29, 882). However, this compound, which is a non-specific inhibitor ofdipeptidyl peptidases, has been shown to be a potent inhibitor of DPIV(Coutts et. al., J. Med. Chem., 1996, 39, 2087). It has beendemonstrated (Cheng, Mol. Cancer Ther., 2005, 4, 351) that FAP-driventumour growth can be attenuated using ValboroPro; this effect isunlikely to be due to DPIV inhibition suggesting that FAP plays animportant role in the promotion of tumour growth. ValboroPro has alsobeen shown to stimulate the growth of hematopoietic progenitorcells andto accelerate neutrophil and erythrocyte regeneration, this regenerationwas observed in DPIV knock-out mice (Jones, Blood, 2003, 102, 150).

Inhibitors of DPIV are at present in clinical trials for treatment oftype II diabetes. Of the many reported inhibitors of DPIV one class ofcompound reported are the aminoacyl pyrrolidine nitriles (Evans, IDrugs,2002, 5, 577). However, these fall into two distinct classes; those withan unsubstituted amino group at the N-terminus (WO 9515309, WO 0181337,WO 0181304), and the N-allylglycine derivatives (WO 0196295). No datahas been reported for the activity of these compounds as FAP inhibitors.There are no reports of DPIV inhibitors with an N-acyl or N-carbamoylN-terminus.

Whilst inhibitors of prolyl ologopeptidases (which have endopeptidaseactivity) are known, they appear not to have been reported as showingany activity against cancer in clinical testing.

According to an aspect, the present invention aims at providing active,selective FAP inhibitors, preferably without DPIV inhibition.Preferably, the compounds are easy to synthesize. More preferably, theyare orally available.

DISCLOSURE OF THE INVENTION

According to an aspect, the present invention relates to the compoundsof claim 1.

The term “alkyl” includes saturated hydrocarbon residues including:

-   -   linear groups up to 10 atoms (C₁-C₁₀). Examples of such alkyl        groups include, but are not limited, to C₁-methyl, C₂-ethyl,        O₃-propyl and C₄-n-butyl;    -   branched groups of between 3 and 10 atoms (C₃-C₁₀). Examples of        such alkyl groups include, but are not limited to,        C₃-iso-propyl, O₄-sec-butyl, C₄ iso-butyl, C₄-tert-butyl and        C₅-neo-pentyl;    -   cyclic groups of between 3 and 8 atoms (C₃-C₈). Examples of such        groups include, but are not limited to, C₃-cyclopropyl,        C₄-cyclobutyl, C₅-cyclopentyl and C₆-cyclohexyl;    -   combinations of linear, branched and cyclic groups. Examples of        such groups include, but are not limited to,

The term “alkenyl” includes monounsaturated hydrocarbon residuesincluding:

-   -   linear groups of between 2 and 6 atoms (C₂-C₆). Examples of such        alkenyl groups include, but are not limited to, C₂-vinyl,        C₃-1-propenyl, C₃-allyl and C₄-2-butenyl;    -   branched groups of between 3 and 8 atoms (C₃-C₈). Examples of        such alkenyl groups include, but are not limited to,        C₄-2-methyl-2-propenyl and C₆-2,3-dimethyl-2-butenyl;    -   cyclic groups of between 3 and 8 atoms (C₃-C₈). Examples of such        groups include, but are not limited to, C₅-3-cyclopentenyl and        C₆-1-cyclohexenyl.

The term “aryl” includes optionally substituted phenyl and optionallysubstituted naphthyl. Examples of such aryl groups include, but are notlimited to, phenyl, 2-tolyl, 3-chlorophenyl, 4-chlorophenyl,3-fluorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl,2,5-difluorophenyl, 1-naphthyl and 2-naphthyl.

The term “heteroaryl” includes optionally substituted heterocycles. Suchheteroaryl groups include, but are not limited to, pyridyl,2-chloropyridyl, 4-methylpyridyl, thienyl, 3-chlorothienyl,2,3-dimethylthiophenyl, furyl and 2-methylfuryl.

Further aspects of the invention are provided according to the claims.

According to an aspect the compounds of the invention are inhibitors ofFAP. According to an aspect the compounds of the invention are usefulfor the treatment of cancer and/or liver cirrhosis. According to anaspect of the present invention it is envisionaged that at least one FAPinhibitor may be co-administered with at least one known cancer agent.Such anti-cancer agents include the compounds mentioned in claim 12 ofWO2004045593.

According to an aspect, the present invention relates to theparticularly preferred compounds of claim 25. The particularly preferredcompounds are inhibitors of FAP of high activity.

According to an aspect, the invention is further related topharmaceutical compositions incorporating a compound according to theinvention used as a FAP inhibitor; these compositions are particularlyuseful for medical indications such as the treatment of cancer and livercirrhosis.

According to an aspect, the invention concerns the use of a compound ofthe invention for the manufacture of a medicament for the treatment of acondition selected among cancer, liver cirrhosis, malignant and benigntumours, ectopic tissue growth, wound healing, organ fibrosis,cirrhosis, metastasis, blood cell disorders, anemia, andchemotherapy-induced neutropenia.

The compounds according to the present invention are useful fortreatment of several diseases, disorders or conditions. The term“treatment” used herein relates to both treatment in order to cure oralleviate a disease, disorder or a condition, and to treatment in orderto prevent the development of a disease, disorder or a condition. Thetreatment may either be performed in an acute or in a chronic way. Thehuman or animal to be treated, i.e. the patient, may be any human ornon-human mammal in need of treatment according to the invention.

The term “therapeutically effective amount” relates to an amount thatwill lead to the desired therapeutical effect. The therapeuticallyeffective amount will be determined by the attending physician takinginto consideration all appropriate factors. Generally a single dose willcomprise between 0.1 mg and 1000 mg, preferably between 1 mg and 250 mg,of the active compound according to the invention. The dose may be givenon a single occasion or repeatedly. When given repeatedly, it may begiven at regular intervals, such as once, twice or three times daily, oron demand, according to the condition being treated.

According to an aspect, the invention concerns a pharmaceuticalcomposition comprising a compound according to the invention as anactive agent. Any excipients used will depend on the intended nature ofthe formulation, which will, in turn, depend on the intended route ofadministration. Administration may be oral, transmucosal (such assublingual, buccal, intranasal, vaginal and rectal), transdermal or byinjection (such as subcutaneous, intramuscular and intravenous). Oraladministration is generally preferred. For oral administration, theformulation may be a tablet, a capsule or a sachet.

The pharmaceutical composition according to an aspect of the presentinvention may be presented in any form that is known in the art. Forexample, the formulation may be presented as a tablet, capsule, powder,suppository, cream, solution or suspension, or in a more complex formsuch as an adhesive patch. The formulation will generally include one ormore excipients, such as diluents, bulking agents, binding agents,dispersants, solvents, preservatives, flavouring agents and the like.

The pharmaceutical composition according to the present invention mayoptionally comprise at least one further additive such as adisintegrating agent, binder, lubricant, flavoring agent, preservative,colorant and a mixture thereof. Representative examples can be found in“Handbook of Pharmaceutical Excipients”; Ed. A. H. Kibbe, 3^(rd) Ed.,American Pharmaceutical Association, USA and Pharmaceutical Press UK,2000.

The compounds of the present invention can be prepared by methodsgenerally known in the art and illustrated in the following non-limitingexamples.

The compounds according to general formula 1 can be prepared usingconventional synthetic methods.

In a first step (Scheme 1) a nitrogen containing heterocycle (5) iscoupled using standard peptide coupling conditions to an alpha aminoacid (6) suitably amino-protected with a standard protecting group suchas tert-butyloxycarbonyl (BOC), benzyloxycarbonyl (Z) or9-fluorenylmethyloxycarbonyl (Fmoc). The use of such groups is wellknown in the art. Where R1 has a reactive functional group such as anamine or a carboxylic acid, this group will also be protected. Theprinciples of functional group protection are well known in the art andare described in, for example, J. F. W. McOmie, “Protective Groups inOrganic Chemistry”, Plenum Press, 1973; T. W. Greene and P. G. M. Wuts,“Protective Groups in Organic Synthesis”, 3^(rd) edition, John Wiley,1999; and P. J. Kocienski, “Protecting groups”, Georg Thieme Verlag,1994.

In a second step when the group A of 7 is a carbamoyl group this isdehydrated to the corresponding nitrile using standard dehydratingconditions such as trifluoroacetic anhydride, or phosphorous oxychloridein pyridine or DMF (Scheme 2). Deprotection using standard methodsfollowed by reaction with an acid chloride or isocyanate in the presenceof base gives the compounds of the invention. Alternatively suchcompounds may be prepared from the deprotected compound by coupling theamine with a carboxylic acid using standard coupling conditions orreacting the amine with a further amine in the presence of CDI orphosgene or diphosgene.

Alternatively in a second step the intermediate 7 can be deprotectedusing standard methods and reacted with an acid chloride or isocyanatein the presence of base (Scheme 3). Alternatively such compounds may beprepared from the deprotected compound by coupling the amine with acarboxylic acid using standard coupling conditions or reacting the aminewith a further amine in the presence of CDI or phosgene or diphosgene.

When the group A of 8 is a carbamoyl group this is dehydrated to anitrile using standard dehydrating conditions such as trifluoroaceticanhydride, or phosphorous oxychloride in pyridine or DMF giving thecompounds of the invention (Scheme 4).

When the group A of 8 is a hydroxymethyl group this is oxidised to analdehyde 9, using an oxidising agent such as Dess Martin Periodinanegiving the compounds of the invention (Scheme 5).

The aldehyde 9 can be further manipulated to give ketones (Scheme 6).This involves reaction of the aldehyde with organometallic reagents suchas Grignard reagents or lithiated aromatics and heteroaromatics and thesubsequent oxidation of the resulting alcohol using an oxidising agentsuch as Dess Martin Periodinane giving the compounds of the invention.

An alternative route to the ketones starts from a nitrogen containingheterocycle-2-carboxaldehyde suitably amino-protected with a standardprotecting group such as tert-butyloxycarbonyl (BOC), benzyloxycarbonyl(Z) or 9-fluorenylmethyloxycarbonyl (Fmoc). The use of such groups iswell known in the art. In a first step the aldehyde is reacted withorganometallic reagents such as Grignard reagents or lithiated aromaticsand heteroaromatics (Scheme 7). The protecting group is removed bystandard methods giving compound 10.

An alpha amino acid suitably carboxyl-protected with a standardprotecting group is reacted with an acid chloride or isocyanate in thepresence of base (Scheme 8). Alternatively such compounds may beprepared from the deprotected compound by coupling the amine with acarboxylic acid using standard coupling conditions or reacting the aminewith a further amine in the presence of CDI or phosgene or diphosgene.The carboxylic acid is protected as an ester such as methyl, benzyl ortert-butyl. The use of such groups is well known in the art. Where R1has a reactive functional group such as an amine or a carboxylic acid,this group will also be protected. After deprotection using standardmethodology the resulting acid is coupled with the amine 10 usingstandard coupling methodology. Subsequent oxidation of the resultingalcohol using an oxidising agent such as Dess Martin Periodinane givesthe compounds of the invention.

When the A group of 8 is a boronic acid this is protected as an ester byprotecting groups described in the literature such as pinanediol esters.This protecting group is removed by methods described in the literaturesuch as sodium metaperiodate/ammonium acetate or phenylboronic acidgiving the compounds of the invention (Scheme 9).

When the R3 group of the alpha amino acid 6 is not hydrogen the requiredamino acid is prepared from the carboxyl protected amino acid byreductive amination of the free amino group with an aldehyde and eithersodium cyanoborohydride or sodium triacetoxyborohydride or similarreagent (Scheme 10) This is followed by protection of the amino functionand deprotection of the carboxyl function using standard methods to givethe required amino acids. The carboxylic acid is protected as an estersuch as methyl, benzyl or tert-butyl. The amine is protected with astandard protecting group such as tert-butyloxycarbonyl (BOC),benzyloxycarbonyl (Z) or 9-fluorenylmethyloxycarbonyl (Fmoc). The use ofsuch groups is well known in the art. Where R1 has a reactive functionalgroup such as an amine or a carboxylic acid, this group will also beprotected

The nitrogen containing heterocycle derivatives are either knowncompounds or can be prepared by simple modification of publishedsynthetic routes.

The general methods are further illustrated in the following,non-limiting examples. These examples shall not be construed as alimitation of how the invention may be practiced.

Examples of Q being CN are provided in Examples E1-E24, E34-E61 andTables 1-23. Examples of Q being B(OH)₂ are provided in ExamplesE29-E30. Examples of Q being C(═O)X¹ are provided in Examples E31-E33and E62-E66. Examples of Q being H are provided in Examples E25-E28 andTables 24-25.

All citations are incorporated by reference.

The compounds were tested for protease (FAP, DPIV, DP8 and DP9)inhibitory activity using a fluorogenic assay utilising dipeptide-AFCsubstrates. For example, DPIV inhibitory activity was measured usingH-Ala-Pro-AFC as a substrate using a method described in WO 9515309. Theparticularly preferred compounds were competitive inhibitors with IC₅₀of <1 μM for FAP and IC₅₀>1 μM for DPIV, DP8 and DP9.

The following abbreviations have been used:

-   Bu Butyl-   Ch Cyclohexyl-   DMF N,N-Dimethylformamide-   Fmoc 9-Fluorenylmethyloxycarbonyl-   h Hours-   Hex Hexyl-   HBTU 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium    hexafluorophosphate-   iBu Iso-Butyl-   iPr Iso-Propyl-   min Minutes-   MS Mass spectrum    -   Nuclear magnetic resonance spectrum—NMR-   NMR spectra were recorded at a frequency of 270 MHz unless otherwise    indicated-   Oic Octahydroindole-2-carboxyl-   Pet. Petroleum ether fraction boiling at 60-   ether 80° C.

Pic Pipecolinyl

-   Pr Propyl-   PyBOP® Benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium    hexafluorophosphate-   PyBroP® Bromo-tris-pyrrolidino-phosphonium hexafluorophosphate-   THF Tetrahydrofuran-   Tic 1,2,3,4-Tetrahydroisoquinoline-3-carboxyl

EXAMPLE E1(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrileA.(2S)-1-((2′S)-2′-(tert-Butyloxycarbonylamino)-3′-methylpentanoyl)pyrrolidine-2-carboxamide

N^(α)-(tert-Butyloxycarbonyl)-L-isoleucine (4.2 g, 18.2 mmol) wasdissolved in CH₂Cl₂/DMF (9:1, 100 ml). The solution was cooled to 0° C.,L-prolinamide (2.5 g, 21.7 mmol), 1-hydroxybenzotriazole hydrate (4.9 g,36.2 mmol) and water soluble carbodiimide (4.4 g, 22.0 mmol) were addedand after 15 min the pH adjusted to pH9 with triethylamine. After 18 hat 0° C. to room temperature the solvent was removed in vacuo and theresidue was taken up in ethyl acetate (200 ml). The solution was washedwith 0.3M KHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) andevaporated in vacuo. The residue was purified by flash chromatography(eluant: 2% methanol, 98% chloroform) to give a colourless oilidentified as the title compound (4.8 g, 14.58 mmol, 80%).

B.(2S)-1-((2′S)-2′-(tert-Butyloxycarbonylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(tert-Butyloxycarbonylamino)-3-methylpentanoyl)pyrrolidine-2-carboxamide(4.8 g, 14.58 mmol) was dissolved in dry THF (100 ml). The solution wascooled to 0° C., triethylamine (2.8 g, 28 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (6.8 g, 32.4 mmol). ThepH was adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml). The solution was washedwith 0.3M KHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) andevaporated in vacuo. The residue was purified by flash chromatography(eluant: 60% Pet. ether, 40% ethyl acetate) to give a colourless oilidentified as the title compound (3.4 g, 11.0 mmol, 75%).

C.(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(tert-Butyloxycarbonylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile(1.51 g, 4.88 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (980 mg, 9.8 mmol) was added followed by 2-anisoylchloride (920 mg, 5.4 mmol). After 18 h at 0° C. to room temperature thesolvent was removed in vacuo and the residue dissolved in ethyl acetate(200 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, waterand brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 60% Pet. ether, 40% ethylacetate) to give a colourless oil identified as the title compound (1.53g, 4.46 mmol, 91%).

EXAMPLE E2(2S)-1-((2′S)-2′-(Ethylcarbamoylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(tert-Butyloxycarbonylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile(3.28 g, 10.2 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (2.5 g, 25 mmol) was added followed by ethylisocyanate(810 mg, 11.4 mmol). After 18 h at 0° C. to room temperature the solventwas removed in vacuo and the residue dissolved in ethyl acetate (200ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue wasrecrystallised from Pet. ether and ethyl acetate to give a white solididentified as the title compound (2.58 g, 9.21 mmol, 87%).

EXAMPLE E3(2S)-1-((2′S)-2′-(3-Methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-Amino-3-methylpentanoyl)pyrrolidine-2-carbonitrilehydrochloride (50 mg, 0.2 mmol) was dissolved in CH₂Cl₂ (100 ml). Thesolution was cooled to 0° C., triethylamine (50 mg, 0.5 mmol) was addedfollowed by 3-anisoyl chloride (38 mg, 0.22 mmol). After 18 h at 0° C.to room temperature the solvent was removed in vacuo and the residuedissolved in ethyl acetate (200 ml). This solution was washed with 0.3MKHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated invacuo. The residue was purified by flash chromatography (eluant: 60%Pet. ether, 40% ethyl acetate) to give a colourless oil identified asthe title compound (59 mg, 0.17 mmol, 86%).

EXAMPLE E4(2S)-1-((2′S)-2′-(4-Methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-Amino-3-methylpentanoyl)pyrrolidine-2-carbonitrilehydrochloride (50 mg, 0.2 mmol) was dissolved in CH₂Cl₂ (100 ml). Thesolution was cooled to 0° C., triethylamine (50 mg, 0.5 mmol) was addedfollowed by 4-anisoyl chloride (38 mg, 0.22 mmol). After 18 h at 0° C.to room temperature the solvent was removed in vacuo and the residuedissolved in ethyl acetate (200 ml). This solution was washed with 0.3MKHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated invacuo. The residue was purified by flash chromatography (eluant: 60%Pet. ether, 40% ethyl acetate) to give a colourless oil identified asthe title compound (46 mg, 0.13 mmol, 67%).

EXAMPLE E5(2S)-1-((2′S)-2′-(Pivaloylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-Amino-3-methylpentanoyl)pyrrolidine-2-carbonitrilehydrochloride (50 mg, 0.2 mmol) was dissolved in CH₂Cl₂ (100 ml). Thesolution was cooled to 0° C., triethylamine (50 mg, 0.5 mmol) was addedfollowed by pivaloyl chloride (24 mg, 0.20 mmol). After 18 h at 0° C. toroom temperature the solvent was removed in vacuo and the residuedissolved in ethyl acetate (200 ml). This solution was washed with 0.3MKHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated invacuo. The residue was purified by flash chromatography (eluant: 60%Pet. ether, 40% ethyl acetate) to give a colourless oil identified asthe title compound (37 mg, 0.13 mmol, 63%).

EXAMPLE E6(2S)-1-((2′S)-1′-(3-Methoxybenzoyl)pyrrolidine-2′-carbonyl)pyrrolidine-2-carbonitrileA.(2S)-1-((2′S)-1′-(tert-Butyloxycarbonylamino)pyrrolidine-2′-carbonyl)pyrrolidine-2-carboxamide

N^(α)-(tert-Butyloxycarbonyl)-L-proline (5.0 g, 23.26 mmol) wasdissolved in CH₂Cl₂/DMF (9:1, 100 ml). The solution was cooled to 0° C.,L-prolinamide (2.9 g, 25.2 mmol) 1-hydroxybenzotriazole hydrate (6.3 g,46.7 mmol) and water soluble carbodiimide (5.6 g, 28.0 mmol) were addedand after 15 min the pH adjusted to pH9 with triethylamine. After 18 hat 0° C. to room temperature the solvent was removed in vacuo and theresidue was taken up in ethyl acetate (200 ml). This solution was washedwith 0.3M KHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) andevaporated in vacuo. The residue was purified by flash chromatography(eluant: 9% methanol, 91% chloroform) to give a colourless oilidentified as the title compound (5.36 g, 17.2 mmol, 74%).

B. (2S)-1-((2′S)-1′-(tert-Butyloxycarbonylamino)pyrrolidine-2′-carbonyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-1-(tert-Butyloxycarbonylamino)pyrrolidine-2-carbonyl)pyrrolidine-2-carboxamide (5.26 g, 16.4 mmol) wasdissolved in dry THF (100 ml). The solution was cooled to 0° C.,triethylamine (3.3 g, 33 mmol) was added followed by the slow additionof trifluoroacetic anhydride (7.8 g, 37.1 mmol). The pH was adjusted topH9 with triethylamine. After 30 min the reaction mixture was dilutedwith ethyl acetate (100 ml), washed with water and brine, dried (Na₂SO₄)and evaporated in vacuo. The residue was purified by flashchromatography (eluant: 4% methanol, 96% chloroform) to give acolourless oil identified as the title compound (3.9 g, 13.3 mmol, 79%).

C.(2S)-1-((2′S)-1′-(3-Methoxybenzoyl)pyrrolidine-2-carbonyl)pyrrolidine-2′-carbonitrile

(2S)-1-((2S)-1-(tert-Butyloxycarbonylamino)pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile(3.8 g, 12.9 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (2.7, 27 mmol) was added followed by 3-anisoyl chloride(2.51 g, 14.7 mmol). After 18 h at 0° C. to room temperature the solventwas removed in vacuo and the residue dissolved in ethyl acetate (200ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 3% methanol, 97% chloroform) to give anorange oil identified as the title compound (3.6 g, 11.6 mmol, 85%).

EXAMPLE E7(2S)-1-((2′S)-1′-(Isopropylcarbamoyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-1-(tert-Butyloxycarbonylamino)pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile(1.43 g, 4.88 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (980 mg, 9.8 mmol) was added followed byisopropylisocyanate (515 mg, 6.65 mmol). After 18 h at 0° C. to roomtemperature the solvent was removed in vacuo and the residue dissolvedin ethyl acetate (200 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 4% methanol,96% chloroform) to give a colourless oil identified as the titlecompound (1.29 g, 4.65 mmol, 95%).

EXAMPLE E8(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′,3′-dimethylbutanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-Amino-3,3-dimethylbutanoyl)pyrrolidine-2-carbonitrilehydrochloride (150 mg, 0.61 mmol; prepared according to Jenkins et al.,WO 9515309) was dissolved in CH₂Cl₂ (40 ml). The solution was cooled to0° C., triethylamine (120 mg, 1.2 mmol) was added followed by 2-anisoylchloride (120 mg, 0.7 mmol). After 18 h at 0° C. to room temperature thesolvent was removed in vacuo and the residue dissolved in ethyl acetate(200 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, waterand brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 60% Pet. ether, 40% ethylacetate) to give a white solid identified as the title compound (172 mg,0.5 mmol, 82%).

EXAMPLE E9(2S)-1-((2′S)-1′-(3-Chlorobenzoyl)pyrrolidine-2′-carbonyl)pyrrolidine-2-carbonitrileA. Synthesis of Fmoc-Pro-Sieber Resin

Fmoc-Sieber resin (1 g, 0.6 mmol/g substitution) was swollen with CH₂Cl₂for 10 min. The resin was further washed with DMF three times. TheFmoc-group was removed with 20% piperidine in DMF for 30 min. Furtherrepeated washings were done with DMF (3×2 min), CH₂Cl₂ (3×2 min), andDMF (1×1 min). Then Fmoc-L-proline (1.5 mmol, 2.5 equivalents withrespect to resin loading), PyBop® (1.5 mmol) and diisopropylethylamine(3.0 mmol) together in DMF (10 ml) were added to the resin. The resinwas shaken at room temperature for 60 min. A small sample of resin wassubjected to Kaiser test for the completion of reaction. The resin wasfiltered and washed with DMF (3×2 min), CH₂Cl₂ (2×2 min), MeOH (2×2min), CH₂Cl₂ (2×2 min) and MeOH (3×2 min).

B. Synthesis of Fmoc-Pro-Pro-Sieber Resin

Resin from step A was swollen with CH₂Cl₂ (1×10 min) then further washedwith DMF three times. The Fmoc group was removed with 20% piperidine inDMF for 30 min. Further resin washings were done with DMF (3×2 min),CH₂Cl₂ (3×2 min) and DMF (1×1 min). Then Fmoc-L-Proline (1.5 mmol, 2.5equivalents with respect to initial resin loading), PyBop® (1.5 mmol)and diisopropylethylamine (3 mmol) together in DMF (10 ml) were added tothe resin. The resin was shaken at room temperature for 60 min. A smallsample of resin was submitted for isatin test for completion ofreaction. The resin was filtered and washed with DMF (3×2 min), CH₂Cl₂(2×2 min), MeOH (2×2 min), CH₂Cl₂ (2×2 min) and MeOH (3×2 min).

C. Synthesis of 3-chlororobenzoyl-Pro-Pro-Sieber Resin

Resin from step B was swollen with CH₂Cl₂ (1×10 min). The resin wasfurther washed with DMF three times. The Fmoc group was removed with 20%piperidine in DMF for 30 min. Further resin washings were done with DMF(3×2 min) and CH₂Cl₂ (3×2 min). Then 3-chlorobenzoyl chloride (1.5 mmol,2.5 equivalents with respect to original resin loading) anddiisopropylethylamine (3 mmol) were added in CH₂Cl₂ (10 ml) were addedto the resin. The resin was shaken at room temperature for 18 h. A smallsample was subjected to isatin test for completion of reaction. Theresin was filtered and washed with CH₂Cl₂ (3×2 min), MeOH (2×2 min),CH₂Cl₂ (2×2 min), and MeOH (2×2 min).

D.(2S)-1-((2′S)-1′-(3-Chlorobenzoyl)pyrrolidine-2′-carbonyl)pyrrolidine-2-carbonitrile

Resin from step C was swollen with CH₂Cl₂ (12 ml). Then trifluoroaceticanhydride (3 mmol, 5 equivalents with respect to initial resin) andpyridine (6 mmol) were added to the resin. The resin shaken at roomtemperature for 18 h. Resin filtered, washed CH₂Cl₂. The solvent wasremoved in vacuo and the residue dissolved in ethyl acetate (70 ml).This solution was washed with 0.3M KHSO₄, water, 1M NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo, the residue waslyophilised from acetonitrile/water to yield an orange oil identified asthe title compound (150 mg, 0.45 mmol).

EXAMPLE E10(2S)-1-((2′S)-2′-(3-Methoxybenzoylamino)-4′-methylpentanoyl)pyrrolidine-2-carbonitrileA. Synthesis of Boc-Leu-Pro-Sieber Resin

2 g of resin synthesised as described for step A of Example E9 wasswollen with CH₂Cl₂ (1×10 min) then further washed with DMF three times.The Fmoc group was removed with 20% piperidine in DMF for 30 min.Further resin washings were done with DMF (3×2 min), CH₂Cl₂ (3×2 min)and DMF (1×1 min). Then Boc-L-leucine (3 mmol, 2.5 equivalents withrespect to initial resin loading), PyBop® (3 mmol) anddiisopropylethylamine (6 mmol) together in DMF (20 ml) were added to theresin. The resin was shaken at room temperature for 60 min. A smallsample of resin was submitted for isatin test for completion ofreaction. The resin was filtered and washed with DMF (3×2 min), CH₂Cl₂(2×2 min), MeOH (2×2 min), CH₂Cl₂ (2×2 min) and MeOH (3×2 min).

B.(2S)-1-((2′S)-2′-(tert-Butyloxycarbonylamino)-4′-methylpentanoyl)pyrrolidine-2-carbonitrile

Resin from step C was swollen with CH₂Cl₂ (6 ml). Then trifluoroaceticanhydride (6 mmol, 5 equivalents with respect to initial resin) and 12mmol of pyridine were added to the resin. Resin shaken at roomtemperature for 18 h. Resin filtered, washed CH₂Cl₂. The solvent wasremoved in vacuo and the residue dissolved in ethyl acetate (70 ml).This solution was washed with 0.3M KHSO₄, water, 1M NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo, the residue waslyophilised from acetonitrile/water to yield an orange oil identified asthe title compound (220 mg, 0.72 mmol, 60%).

C.(2S)-1-((2′S)-2′-(3-Methoxybenzoylamino)-4′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(tert-Butyloxycarbonylamino)-4-methylpentanoyl)pyrrolidine-2-carbonitrile(50 mg, 0.16 mmol) was treated with trifluoroacetic acid (5 ml). After 1h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (5 ml). The solution was cooled to 0° C.,triethylamine (32 mg, 0.32 mmol) was added followed by 3-anisoylchloride (30 mg, 0.176 mmol). After 18 h at 0° C. to room temperaturethe solvent was removed in vacuo and the residue dissolved in ethylacetate (70 ml). This solution washed with 0.3M KHSO₄, sat. NaHCO₃,water and brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 60% Pet. ether, 40% ethylacetate) to give a colourless oil identified as the title compound (35mg, 0.10 mmol, 64%).

EXAMPLE E11(2S)-1-((2′S)-2′-(2″-Phenylethylthiocarbamoylamino)-3′-methylpentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-Amino)-3-methylpentanoyl)pyrrolidine-2-carbonitrilehydrochloride (75 mg, 0.3 mmol) was dissolved in CH₂Cl₂ (20 ml). To thissolution was added triethylamine (100 mg, 1.0 mmol) followed by2-phenylethylisothiocyanate (50 mg, 0.31 mmol). After 18 h at roomtemperature the solvent was removed in vacuo and the residue dissolvedin ethyl acetate (70 ml). This solution was washed with 0.3M KHSO₄, sat.NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo. Theresidue was purified by flash chromatography (eluant: 20% Pet. ether,80% ethyl acetate) to give a white solid identified as the titlecompound (86 mg, 0.23 mmol, 76%).

EXAMPLE E12(2S)-1-((2′S)-1′-(Propylthiocarbamoyl)pyrrolidine-2′-carbonyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-1-(2-tert-Butyloxycarbonylamino)pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile(160 mg, 0.55 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (20 ml). Triethylamine (150 mg, 1.5 mmol) was addedfollowed by n-propylisothiocyanate (55 mg, 0.5 mmol). After 18 h at roomtemperature the solvent was removed in vacuo and the residue dissolvedin ethyl acetate (70 ml). This solution was washed with 0.3M KHSO₄, sat.NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo. Theresidue was purified by flash chromatography (eluant: 20% Pet. ether,80% ethyl acetate) to give a white solid identified as the titlecompound (55 mg, 0.19 mmol, 34%).

EXAMPLE E13(2S)-1-(2′-(N-(2-Methoxybenzoyl)-N-(2-methylpropyl)amino)acetyl)pyrrolidine-2-carbonitrileA. N^(α)-(2-Methylpropyl)glycine methyl ester

Glycine methylester hydrochloride (2.0 g, 16.0 mmol) was dissolved inMeOH/AcOH (9:1, 25 ml). Triethylamine (1.8 g, 18.0 mmol) was addedfollowed by 2-butanone (1.3 g, 18.0 mmol). After 2 h at room temperaturesodium triacetoxyborohydride (3.81 g, 18.0 mmol) was added. After 18 hat room temperature the solvent was removed in vacuo and the residue wastaken up in chloroform (200 ml). This solution was washed with sat.NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo to givea colourless oil identified as the title compound (646 mg, 4.46 mmol,28%).

B. N^(α)-(tert-Butyloxycarbonyl)-N^(α)-(2-methylpropyl) glycine methylester

N)-(2-Methylpropyl)glycine methyl ester (646 mg, 4.45 mmol) wasdissolved in CH₂Cl₂ (25 ml). Triethylamine (560 mg, 5.6 mmol) was addedfollowed by di-tertbutyl dicarbonate (1.07 g, 4.90 mmol). After 18 h atroom temperature N,N-dimethylethylenediamine (1 ml) was added, thesolvent was removed in vacuo and the residue was taken up in chloroform(100 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, waterand brine, dried (Na₂SO₄) and evaporated in vacuo to give an amber oilidentified as the title compound (960 mg, 3.92 mmol, 88%).

C. N^(α)-(tert-Butyloxycarbonyl)-N^(α)-(2-methylpropyl) glycine

N^(α)-(tert-Butyloxycarbonyl)-N^(α)-(2-methylpropyl) glycine methylester (960 mg, 3.91 mmol) was dissolved in THF/H₂O (9:1, 25 ml). Lithiumhydroxide monohydrate (492 mg, 11.7 mmol) was added. After 18 h at roomtemperature the reaction mixture was diluted with ethyl acetate (100ml). This solution was washed with 1M HCl, water and brine, dried(Na₂SO₄) and evaporated in vacuo to give a colourless oil identified asthe title compound (360 mg, 1.56 mmol, 40%).

D.(2S)-1-(2′-(N-tert-Butyloxycarbonyl-N-(2-methylpropyl)amino)acetyl)pyrrolidine-2-carboxamide

N^(α)-(tert-Butyloxycarbonyl)-N^(α)-(2-methylpropyl) glycine (360 mg,1.56 mmol) was dissolved in CH₂Cl₂/DMF (9:1, 20 ml). The solution wascooled to 0° C., L-prolinamide hydrochloride (282 mg, 1.87 mmol),1-hydroxybenzotriazole hydrate (295 mg, 2.18 mmol) and water solublecarbodiimide (358 mg, 1.87 mmol) were added and after 15 min the pHadjusted to pH9 with triethylamine. After 18 h at 0° C. to roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (100 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 4% methanol,94% chloroform, 2% triethylamine) to give a colourless oil identified asthe title compound (330 mg, 1.01 mmol, 65%).

E.(2S)-1-(2′-(N-tert-Butyloxycarbonyl-N-(2-methylpropyl)amino)acetyl)pyrrolidine-2-carbonitrile

(2S)-1-(2-(N-tert-Butyloxycarbonyl-N-(2-methylpropyl)amino)acetyl)pyrrolidine-2-carboxamide(330 mg, 1.01 mmol) was dissolved in dry THF (20 ml). The solution wascooled to 0° C., triethylamine (210 mg, 2.1 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (460 g, 2.2 mmol). The pHwas adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml), washed with water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 3% methanol, 97% chloroform) to give anorange oil identified as the title compound (156 mg, 0.50 mmol, 50%).

F.(2S)-1-(2′-(N-(2-Methoxybenzoyl)-N-(2-methylpropyl)amino)acetyl)pyrrolidine-2-carbonitrile

(2S)-1-(2-(N-tert-Butyloxycarbonyl-N-(2-methylpropyl)amino)acetyl)pyrrolidine-2-carbonitrile(25 mg, 0.081 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (30 mg, 0.3 mmol) was added followed by 2-anisoyl chloride(15 mg, 0.088 mmol). After 18 h at 0° C. to room temperature the solventwas removed in vacuo and the residue dissolved in ethyl acetate (200ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 2% methanol, 98% chloroform) to give acolourless oil identified as the title compound (18 mg, 0.052 mmol,66%).

EXAMPLE E14(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-5′-amino-pentanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-5-(9-fluorenylmethyloxycarbonylcarbonylamino) pentanoyl)pyrrolidine-2-carbonitrile (200 mg, 0.35 mmol)prepared by the method described for Example E10 was dissolved inacetonitrile (10 ml), diethylamine (10 ml) was added. After 90 min atroom temperature the solvent was removed in vacuo. The residue waspurified by flash chromatography (eluant: 1% triethylamine, 5% methanol,94% chloroform) to give a colourless oil identified as the titlecompound (99 mg, 0.28 mmol, 80%).

EXAMPLE E15(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-6′-amino-hexanoyl)pyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-6-(9-fluorenylmethyloxycarbonylcarbonylamino) hexanoyl)pyrrolidine-2-carbonitrile (176 mg, 0.3 mmol)prepared by the method described for Example E10 was dissolved inacetonitrile (10 ml), diethylamine (10 ml) was added. After 90 min atroom temperature the solvent was removed in vacuo. The residue waspurified by flash chromatography (eluant: 1% triethylamine, 5% methanol,94% chloroform) to give a colourless oil identified as the titlecompound (78 mg, 0.22 mmol, 73%).

EXAMPLE E16(4R)-1-((2′S)-2′-(3-Methoxybenzoylamino)-3′-methylpentanoyl)thiazolidine-4-carbonitrileA. (4R)-3-(tert-Butyloxycarbonyl)thiazolidine-4-carboxamide

(4R)-3-(tert-Butyloxycarbonyl)thiazolidine-4-carboxylic acid (12.5 g,54.1 mmol) was dissolved in CH₂Cl₂/DMF (9:1, 150 ml). To this solutionat 0° C. was added 1-hydroxybenzotriazole hydrate (14.6 g, 108 mmol) andwater-soluble carbodiimide (13.0 g, 65 mmol). After 1 h at 0° C. ammonia(35%, 50 ml) was added. After 18 h at 0° C. to room temperature thesolvent was removed in vacuo and the residue was taken up in ethylacetate (500 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃,water and brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 2% methanol, 98% chloroform)to give a colourless oil identified as the title compound (8.9 g, 38.4mmol, 71%).

B. (4R)-Thiazolidine-4-carboxamide hydrochloride

(4R)-3-(tert-Butyloxycarbonyl)thiazolidine-4-carboxamide (8.6 g, 37.1mmol) was dissolved in 4M HCl/dioxan (50 ml). After 1 h at roomtemperature the solvent was evaporated in vacuo to give a white solididentified as the title compound (6.2 g, 36.8 mmol, 99%).

C.(4R)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)-thiazolidine-4-carboxamide

N^(α)-(tert-Butyloxycarbonyl)-L-isoleucine (1.37 g, 5.9 mmol) wasdissolved in CH₂Cl₂/DMF (9:1, 100 ml). The solution was cooled to 0° C.,(4R)-thiazolidine-4-carboxamide hydrochloride (1 g, 5.9 mmol),1-hydroxybenzotriazole hydrate (920 mg, 6.8 mmol) and water solublecarbodiimide (1.4 g, 7.0 mmol) were added and after 15 min the pHadjusted to pH9 with triethylamine. After 18 h at 0° C. to roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (200 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 4% methanol,96% chloroform) to give a colourless oil identified as the titlecompound (1.65 g, 4.8 mmol, 82%).

D.(4R)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)thiazolidine-4-carbonitrile

((4R)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)thiazolidine-4-carboxamide(1.3 g, 3.76 mmol) was dissolved in dry THF (100 ml). The solution wascooled to 0° C., triethylamine (750 mg, 7.5 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (1.7 g, 8.1 mmol). The pHwas adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml), washed with water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 80% Pet. ether, 20% ethyl acetate) togive a yellow oil identified as the title compound (321 mg, 0.98 mmol,26%).

E.(4R)-1-((2′S)-2′-(3-Methoxybenzoylamino)-3′-methylpentanoyl)thiazolidine-4-carbonitrile

(4R)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)thiazolidine-4-carbonitrile(50 mg, 0.15 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (40 mg, 0.4 mmol) was added followed by 3-anisoyl chloride(26 mg, 0.15 mmol). After 18 h at 0° C. to room temperature the solventwas removed in vacuo and the residue dissolved in ethyl acetate (200ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 60% Pet. ether, 40% ethyl acetate) togive a colourless oil identified as the title compound (20 mg, 0.055mmol, 37%).

EXAMPLE E17(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrileA. Methyl-(2S)—N-(tert-butyloxycarbonyl)pyrrolid-4-one-2-carboxylate

N-(tert-Butyloxycarbonyl)-L-4-trans-hydroxyproline methyl ester (2.5 g,10.2 mmol) was dissolved in CH₂Cl₂ (70 ml). Dess-Martin periodinane (5.0g, 12.1 mmol) was added. After 3 h at room temperature the solvent wasremoved in vacuo and the residue was taken up in ethyl acetate (300 ml).This solution was washed with sat. NaHCO₃, water and brine, dried(Na₂SO₄) and evaporated in vacuo. The residue was purified by flashchromatography (eluant: 10% ethyl acetate, 90% Pet. ether ° C.) to givea colourless oil identified as the title compound (2.4 g, 9.7 mmol,95%).

B. Methyl(2S)—N-(tert-butyloxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylate

Methyl (2S)—N-(tert-butyloxycarbonyl)pyrrolidin-4-one-2-carboxylate (2.3g, 9.3 mmol) was dissolved in CH₂Cl₂ (70 ml). (Diethylamino)sulphurtrifluoride (4.5 g, 27.9 mmol) was added to this solution at 0° C. After18 hs at 0° C. to room temperature the reaction mixture was carefullypoured into sat. NaHCO₃ (100 ml) and stirred for 15 min and extractedwith CH₂Cl₂. The organic extract was washed with water and brine, dried(Na₂SO₄) and evaporated in vacuo. The residue was purified by flashchromatography (eluant: 10% ethyl acetate, 90% Pet. ether ° C.) to givea colourless oil identified as the title compound (2.4 g, 8.9 mmol,96%).

C. (2S)—N-(tert-Butyloxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylicacid

Methyl(2S)—N-(tert-butyloxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylate(2.2 g, 8.3 mmol) was dissolved in THF (100 ml). Aqueous lithiumhydroxide (1M, 10.6 ml, 10.6 mmol) was added. After 3 h at roomtemperature the reaction mixture was diluted with ethyl acetate (150ml), washed with 1M HCl, water, and brine, dried (Na₂SO₄) and evaporatedin vacuo. The residue was purified by flash chromatography (eluant: 95%chloroform, 4% methanol, 1% acetic acid) to give an orange oilidentified as the title compound (2.1 g, 8.3 mmol 100%).

D. (2S)—N-(tert-Butyloxycarbonyl)-4,4-difluoropyrrolidine-2-carboxamide

(2S)—N-(tert-Butyloxycarbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid(1.0 g, 4.0 mmol) was dissolved in CH₂Cl₂/DMF (9:1, 50 ml). To thissolution at 0° C. was added 1-hydroxybenzotriazole hydrate (1.1 g, 8.1mmol) and water soluble carbodiimide (960 mg, 4.8 mmol). After 1 h at 0°C. ammonia (35%, 5 ml) was added. After 18 h at 0° C. to roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (200 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 85% ethylacetate, 15% Pet. ether ° C.) to give a colourless oil identified as thetitle compound (945 mg, 3.8 mmol, 95%).

E.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylbutanoyl)-4,4-difluoropyrrolidine-2-carboxamide

(2S)—N-(tert-Butyloxycarbonyl)-4,4-difluoropyrrolidine-2-carboxamide(530 mg, 2.12 mmol) was dissolved in 4M HCl/dioxan (30 ml) after 1 h atroom temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂/DMF (9:1, 20 ml). To this solution at 0° C. wasadded e-(tert-butyloxycarbonyl)-L-valine (461 mg, 2.12 mmol),1-hydroxybenzotriazole hydrate (401 mg, 2.97 mmol) and water-solublecarbodiimide (487 mg, 2.54 mmol). After 15 min at 0° C. the pH wasadjusted to pH 8 with N,N-disopropylethylamine. After 18 h at 0° C. toroom temperature the reaction mixture was diluted with CHCl₃ (70 ml).This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (Eluant: 97% chloroform, 2% methanol, 1%triethylamine) to give a white solid identified as the title compound(430 mg, 1.23 mmol, 58%).

F.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylbutanoyl)-4,4-difluoropyrrolidine-2-carboxamide(430 mg, 1.23 mmol) was dissolved in dry THF (100 ml). The solution wascooled to 0° C., triethylamine (246 mg, 2.46 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (520 mg, 2.46 mmol). ThepH was adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml), washed with water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 80% Pet. ether, 20% ethyl acetate) togive an orange oil identified as the title compound (323 mg, 0.98 mmol,79%).

G.(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrile(31 mg, 0.09 mmol) was treated with trifluoroacetic acid (10 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (20 ml). The solution was cooled to 0° C.,triethylamine (30 mg, 0.3 mmol) was added followed by 2-anisoyl chloride(18 mg, 0.11 mmol). After 18 h at 0° C. to room temperature the solventwas removed in vacuo and the residue dissolved in ethyl acetate (200ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 80% Pet. ether, 20% ethyl acetate) togive a colourless oil identified as the title compound (14 mg, 0.04mmol, 43%).

EXAMPLE E18(2S)-1-((2′S)-2′-(Ethylcarbamoylamino)-3′-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrile(30 mg, 0.091 mmol) was treated with trifluoroacetic acid (10 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (30 mg, 0.3 mmol) was added followed by ethylisocyanate (8mg, 0.1 mmol). After 18 h at 0° C. to room temperature the solvent wasremoved in vacuo and the residue dissolved in ethyl acetate (200 ml).The solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (eluant: 1% methanol, 99% chloroform) to give acolourless oil identified as the title compound (18 mg, 0.060 mmol,66%).

EXAMPLE E19(2S)-1-((2′S)-1′-(Ethylcarbamoyl)pyrrolidine-2′-carbonyl)-4,4-difluoropyrrolidine-2-carbonitrileA.(2S)-1-((2′S)-1′-(2-tert-Butyloxycarbonylamino)pyrrolidine-2′-carbonyl)-4,4-difluoropyrrolidine-2-carboxamide

(2S)—N-(tert-Butyloxycarbonyl)-4,4-difluoropyrrolidine-2-carboxamide(1.16 g, 4.65 mmol) was dissolved in 4M HCl/dioxan (30 ml) after 1 h atroom temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂/DMF (9:1, 20 ml). To this solution at 0° C. wasadded N^(α)-(tert-butyloxycarbonyl)-L-proline (1.0 g, 4.65 mmol),1-hydroxybenzotriazole hydrate (880 mg, 6.65 mmol) and water solublecarbodiimide (1.07 g, 5.35 mmol). After 15 min at 0° C. the pH wasadjusted to pH 9 with triethylamine. After 18 h at 0° C. to roomtemperature the reaction mixture was diluted with chloroform (70 ml).This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (Eluant: 97% chloroform, 2% methanol, 1%triethylamine) to give a white solid identified as the title compound(698 mg, 2.01 mmol, 43%).

B.(2S)-1-((2′S)-1′-(2-tert-Butyloxycarbonylamino)pyrrolidine-2′-carbonyl)-4,4-difluoropyrrolidine-2-carbonitrile

(2S)-1-((2S)-1-(2-tert-Butyloxycarbonylamino)pyrrolidine-2-carbonyl)-4,4-difluoropyrrolidine-2-carboxamide(698 mg, 2.01 mmol) was dissolved in dry THF (50 ml). The solution wascooled to 0° C., triethylamine (200 mg, 2.0 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (844 mg, 4.02 mmol). ThepH was adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml), washed with water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 80% Pet. ether, 20% ethyl acetate) togive an off-white identified as the title compound (232 mg, 0.708 mmol,35%).

C.(2S)-1-((2′S)-1′-(Ethylcarbamoyl)pyrrolidine-2′-carbonyl)-4,4-difluoropyrrolidine-2-carbonitrile

(2S)-1-((2S)-1-(2-tert-Butyloxycarbonylamino)pyrrolidine-2-carbonyl)-4,4-difluoropyrrolidine-2-carbonitrile(30 mg, 0.09 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (30 mg, 0.3 mmol) was added followed by ethylisocyanate(0.8 mg, 0.01 mmol). After 18 h at 0° C. to room temperature the solventwas removed in vacuo and the residue dissolved in ethyl acetate (200ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 60% Pet. ether, 40% ethyl acetate) togive a colourless oil identified as the title compound (25 mg, 0.083mmol, 92%).

EXAMPLE E20(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)-3,4-dehydropyrrolidine-2-carbonitrileA. (2S)—N-(tert-Butyloxycarbonyl)-3,4-dehydrpyrrolidine-2-carboxamide

(2S)—N-(tert-Butyloxycarbonyl)-3,4-dehydropyrrolidine-2-carboxylic acid(2.0 g, 9.38 mmol) was dissolved in CH₂Cl₂/DMF (9:1, 50 ml). To thissolution at 0° C. was added 1-hydroxybenzotriazole hydrate (1.77 g, 13.1mmol) and water soluble carbodiimide (2.16 g, 11.26 mmol). After 1 h at0° C. ammonia (35%, 7 ml) was added. After 18 h at 0° C. to roomtemperature the reaction mixture was diluted with chloroform (150 ml).This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (eluant: 2% methanol, 98% chloroform) to give awhite solid identified as the title compound (1.58 g, 7.4 mmol, 79%).

B. (2S)-3,4-Dehydropyrrolidine-2-carboxamide hydrochloride

(2S)—N-(tert-Butyloxycarbonyl)-3,4-dehydropyrrolidine-2-carboxamide(1.58 g, 7.44 mmol) was dissolved in 4M HCl/dioxan (50 ml). After 1 h atroom temperature the solvent was evaporated in vacuo to give a whitesolid identified as the title compound (830 mg, 5.58 mmol, 75%).

C.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)-3,4-dehydropyrrolidine-2-carboxamide

N^(α)-(tert-Butyloxycarbonyl)-L-isoleucine (645 mg, 2.79 mmol) wasdissolved in CH₂Cl₂/DMF (9:1, 100 ml). The solution was cooled to 0° C.,(2S)-3,4-dehydropyrrolidine-2-carboxamide hydrochloride (415 mg, 2.79mmol), 1-hydroxybenzotriazole hydrate (528 mg, 3.91 mmol) and watersoluble carbodiimide (642 mg, 3.35 mmol) were added and after 15 min thepH adjusted to pH9 with triethylamine. After 18 h at 0° C. to roomtemperature the reaction mixture was diluted with chloroform (100 ml).This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (eluant: 4% methanol, 96% chloroform) to give anamber solid identified as the title compound (648 mg, 1.98 mmol, 71%).

D.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)-3,4-dehydropyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)-3,4-dehydropyrrolidine-2-carboxamide(648 mg, 1.99 mmol) was dissolved in dry THF (100 ml). The solution wascooled to 0° C., triethylamine (398 mg, 3.98 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (836 mg, 3.98 mmol). ThepH was adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml), washed with water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 100% ethyl acetate) to give a paleyellow solid identified as the title compound (408 mg, 1.33 mmol, 67%).

E.(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)-3,4-dehydropyrrolidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)-3,4-dehydropyrrolidine-2-carbonitrile(15 mg, 0.05 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,diisopropylethylamine (15 mg, 0.15 mmol) was added followed by 2-anisoylchloride (9 mg, 0.059 mmol). After 18 h at 0° C. to room temperature thesolvent was removed in vacuo and the residue dissolved in ethyl acetate(200 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, waterand brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 60% Pet. ether, 40% ethylacetate) to give a colourless oil identified as the title compound (12mg, 0.035 mmol, 71%).

EXAMPLE E21(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)piperidine-2-carbonitrileA. (2S)—N-(tert-Butyloxycarbonyl)piperidine-2-carboxamide

(2S)—N-(tert-Butyloxycarbonyl)pipecolinic acid (3.0 g, 13.0 mmol) wasdissolved in CH₂Cl₂/DMF (9:1, 150 ml). To this solution at 0° C. wasadded 1-hydroxybenzotriazole hydrate (2.0 g, 14.8 mmol) and watersoluble carbodiimide (2.74 g, 13.7 mmol). After 1 h at 0° C. ammonia(35%, 25 ml) was added. After 18 h at 0° C. to room temperature thesolvent was removed in vacuo and the residue was taken up in ethylacetate (500 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃,water and brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 4% methanol, 96% chloroform)to give a white solid identified as the title compound (1.7 g, 7.4 mmol,57%).

B. (2S)-Piperidine-2-carboxamide hydrochloride

(2S)—N-(tert-Butyloxycarbonyl)piperidine-2-carboxamide (1.7 g, 7.4 mmol)was dissolved in 4M HCl/dioxan (50 ml). After 1 h at room temperaturethe solvent was evaporated in vacuo to give a white solid identified asthe title compound (1.1 g, 6.7 mmol, 89%).

C.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)piperidine-2-carboxamide

N^(α)-(tert-Butyloxycarbonyl)-L-isoleucine (772 mg, 3.3 mmol) wasdissolved in CH₂Cl₂ (50 ml). The solution was cooled to 0° C.,(2S)-piperidine-2-carboxamide hydrochloride (550 mg, 3.3 mmol) andPyBop® (1.74 g, 3.5 mmol) were added and the pH adjusted to pH9 withtriethylamine. After 18 h at 0° C. to room temperature the solvent wasremoved in vacuo and the residue was taken up in ethyl acetate (200 ml).This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (eluant: 2% methanol, 98% chloroform) to give ayellow oil identified as the title compound (654 mg, 1.9 mmol, 58%).

D.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)piperidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)piperidine-2-carboxamide(654 mg, 1.9 mmol) was dissolved in dry THF (50 ml). The solution wascooled to 0° C., triethylamine (400 g, 4.0 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (880 mg, 4.2 mmol). ThepH was adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml), washed with water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 60% Pet. ether, 40% ethyl acetate) togive a colourless oil identified as the title compound (300 g, 0.93mmol, 49%).

E.(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)piperidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)piperidine-2-carbonitrile(50 mg, 0.15 mmol) was treated with trifluoroacetic acid (50 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (43 mg, 0.43 mmol) was added followed by 2-anisoylchloride (30 mg, 0.18 mmol). After 18 h at 0° C. to room temperature thesolvent was removed in vacuo and the residue dissolved in ethyl acetate(200 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, waterand brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 60% Pet. ether, 40% ethylacetate) to give a colourless oil identified as the title compound (20mg, 0.056 mmol, 38%).

EXAMPLE E22(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)azetidine-2-carbonitrileA. (2S)—N-(tert-Butyloxycarbonyl)azetidine-2-carboxamide

(2S)—N-(tert-Butyloxycarbonyl)-L-azetidine-2-carboxylic acid (3.87 g19.23 mmol) was dissolved in CH₂Cl₂/DMF (9:1, 150 ml). To this solutionat 0° C. was added 1-hydroxybenzotriazole hydrate (3.64 g, 26.92 mmol)and water-soluble carbodiimide (4.42 g, 23.08 mmol). After 1 h at 0° C.ammonia (35%, 15 ml) was added. After 18 h at 0° C. to room temperaturethe solvent was removed in vacuo and the residue was taken up in ethylacetate (500 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃,water and brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 2% methanol, 98% chloroform)to give a colourless oil identified as the title compound (1.14 g, 5.77mmol, 30%).

B. (2S)-Azetidine-2-carboxamide hydrochloride

(2S)—N-(tert-Butyloxycarbonyl)azetidine-2-carboxamide (1.14 g, 5.69mmol) was dissolved in 4M HCl/dioxan (50 ml). After 1 h at roomtemperature the solvent was evaporated in vacuo to give a white solididentified as the title compound (775 mg, 5.63 mmol, 99%).

C.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)azetidine-2-carboxamide

N^(α)-(tert-Butyloxycarbonyl)-L-isoleucine (657 mg, 2.84 mmol) wasdissolved in CH₂Cl₂/DMF (9:1, 100 ml). The solution was cooled to 0° C.,(2S)-azetidine-2-carboxamide hydrochloride (388 mg, 2.84 mmol),1-hydroxybenzotriazole hydrate (538 mg, 3.98 mmol) and water solublecarbodiimide (654 mg, 3.41 mmol) were added and after 15 min the pHadjusted to pH9 with triethylamine. After 18 h at 0° C. to roomtemperature the reaction mixture was diluted with chloroform (200 ml).This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (eluant: 4% methanol, 96% chloroform) to give anorange oil identified as the title compound (620 mg, 1.99 mmol, 70%).

D.(2S)-1-((2′S)-2′-(2-tert-Butyloxycarbonylamino)-3′-methylpentanoyl)azetidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)azetidine-2-carboxamide(620 mg, 1.98 mmol) was dissolved in dry THF (100 ml). The solution wascooled to 0° C., triethylamine (390 mg, 3.9 mmol) was added followed bythe slow addition of trifluoroacetic anhydride (832 mg, 3.96 mmol). ThepH was adjusted to pH9 with triethylamine. After 30 min the reactionmixture was diluted with ethyl acetate (100 ml), washed with water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 3% methanol, 97% chloroform) to give acolourless oil identified as the title compound (354 mg, 1.2 mmol, 61%).

E.(2S)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)azetidine-2-carbonitrile

(2S)-1-((2S)-2-(2-tert-Butyloxycarbonylamino)-3-methylpentanoyl)azetidine-2-carbonitrile(50 mg, 0.168 mmol) was treated with trifluoroacetic acid (10 ml). After1 h at room temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,diisopropylethylamine (50 mg, 0.50 mmol) was added followed by 2-anisoylchloride (28 mg, 0.185 mmol). After 18 h at 0° C. to room temperaturethe solvent was removed in vacuo and the residue dissolved in ethylacetate (200 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃,water and brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 50% Pet. ether, 50% ethylacetate) to give a colourless oil identified as the title compound (10mg, 0.03 mmol, 18%).

EXAMPLE E23(4R)-1-((2′S)-2′-(3-Methoxybenzoylamino)-3′-methylpentanoyl)thiazolidine-4-carbonitrile-S-oxide

(4R)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylpentanoyl)thiazolidine-4-carbonitrile(70 mg, 0.2 mmol) was dissolved in CH₂Cl₂ (20 ml). The solution wascooled to 0° C., 3-chloroperoxybenzoic acid (33 mg, 0.19 mmol) wasadded. After 30 mins at 0° C. the solvent was evaporated in vacuo. Theresidue was purified by flash chromatography (eluant: 20% Pet. ether,80% ethyl acetate) to give an orange oil identified as the titlecompound (14 mg, 0.037 mmol, 19%).

EXAMPLE E24(4R)-1-((2′S)-2′-(3-Methoxybenzoylamino)-3′-methylpentanoyl)thiazolidine-4-carbonitrile-S,S-dioxide

(4R)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylpentanoyl)thiazolidine-4-carbonitrile(70 mg, 0.2 mmol) was dissolved in CH₂Cl₂ (20 ml). The solution wascooled to 0° C., 3-chloroperoxybenzoic acid (170 mg, 1.0 mmol) wasadded. After 18 h at room temperature the reaction mixture was dilutedwith chloroform (70 ml). This solution was washed with sat. NaHCO₃,water and brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 20% Pet. ether, 80% ethylacetate) to give an orange oil identified as the title compound (18 mg,0.045 mmol, 23%).

EXAMPLE E251-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidine A.(2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoic acid tertbutyl ester

L-Isoleucine tertbutyl ester hydrochloride (500 mg, 2.23 mmol) wasdissolved in CH₂Cl₂ (10 ml). Triethylamine (600 g, 6.0 mmol) and2-anisoyl chloride (456 mg, 2.68 mmol) were added. After 18 h at roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (100 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 60% Pet.ether, 40% ethyl acetate) to give a colourless oil identified as thetitle compound (341 mg, 1.06 mmol, 48%).

B. (2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoic acid

(2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoic acid tertbutyl ester(341 mg, 1.06 mmol) was dissolved in trifluoroacetic acid/CH₂Cl₂ (1:1,10 ml). After 2 h at room temperature the solvent was removed in vacuoand the residue was purified by flash chromatography (eluant: 1% aceticacid, 2% methanol, 97% chloroform) to give a colourless oil identifiedas the title compound (242 mg, 0.91 mmol, 86%).

C. 1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidine

(2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoic acid (25 mg, 0.94 mmol)was dissolved in CH₂Cl₂/DMF (9:1, 10 ml). The solution was cooled to 0°C., pyrrolidine (8 mg, 0.113 mmol), 1-hydroxybenzotriazole hydrate (18mg, 0.132 mmol) and water soluble carbodiimide (22 mg, 0.132=1) wereadded and after 15 min the pH adjusted to pH9 with triethylamine. After18 h at 0° C. to room temperature the solvent was removed in vacuo andthe residue was taken up in ethyl acetate (70 ml). This solution waswashed with 0.3M KHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) andevaporated in vacuo. The residue was purified by flash chromatography(eluant: 20% Pet. ether, 80% ethyl acetate) to give an amber oilidentified as the title compound (10 mg, 0.031 mmol, 33%).

EXAMPLE E261-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylpentanoyl)-3,3-difluoropyrrolidide

(2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoic acid (25 mg, 0.94 mmol)was dissolved in CH₂Cl₂/DMF (9:1, 10 ml). The solution was cooled to 0°C., 3,3-difluoropyrrolidine hydrochloride (16 mg, 0.113 mmol),1-hydroxybenzotriazole hydrate (18 mg, 0.132 mmol) and water solublecarbodiimide (22 mg, 0.132 mmol) were added and after 15 min the pHadjusted to pH9 with triethylamine. After 18 h at 0° C. to roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (70 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 50% Pet.ether, 50% ethyl acetate) to give an amber oil identified as the titlecompound (10 mg, 0.028 mmol, 30%).

EXAMPLE E271-(2′S)-1′-(3-Methoxybenzoyl)pyrrolidine-2′-carbonyl)-3-thiazolidine A.(2S)-1-(3-Methoxybenzoylamino)pyrrolidine-2-carboxylic acid benzyl ester

L-Proline benzyl ester hydrochloride (500 mg, 2.073 mmol) was dissolvedin CH₂Cl₂ (10 ml). Triethylamine (600 mg, 6.0 mmol) and 3-anisoylchloride (422 mg, 2.48 mmol) were added. After 18 h at room temperaturethe solvent was removed in vacuo and the residue was taken up in ethylacetate (100 ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃,water and brine, dried (Na₂SO₄) and evaporated in vacuo. The residue waspurified by flash chromatography (eluant: 3% methanol, 97% chloroform)to give a colourless oil identified as the title compound (654 mg, 1.93mmol, 93%).

B. (2S)-1-(3-Methoxybenzoylamino)pyrrolidine-2-carboxylic acid

(2S)-1-(3-Methoxybenzoylamino)pyrrolidine-2-carboxylic acid benzyl ester(654 mg, 1.93 mmol) was dissolved in THF/H₂O (9:1, 10 ml). Lithiumhydroxide monohydrate (243 mg, 5.79 mmol) was added. After 18 h at roomtemperature the reaction mixture was diluted with ethyl acetate (50 ml).This solution was washed with 1M KHSO₄, water and brine, dried (Na₂SO₄)and evaporated in vacuo to give a colourless oil identified as the titlecompound (470 mg, 1.89 mmol, 98%).

C. 1-((2′S)-1′-(3-Methoxybenzoyl)pyrrolidine-2′-carbonyl)-3-thiazolidide

(2S)-1-(3-Methoxybenzoylamino)pyrrolidine-2-carboxylic acid (61 mg,0.245 mmol) was dissolved in CH₂Cl₂/DMF (9:1, 10 ml). To this solutionwas added thiazolidine (8 mg, 0.113 mmol), PyBrop® (126 mg, 0.271 mmol)and diisopropylethylamine (73.5 mg, 0.735 mmol). After 18 h at roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (70 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 3% methanol,97% chloroform) to give an amber oil identified as the title compound(27 mg, 0.084 mmol, 34%).

EXAMPLE E281-((2′S)-1′-(Isopropylcarbamoyl)pyrrolidine-2′-carbonyl)pyrrolidine A.(2S)-1-(Isopropylcarbamoyl)pyrrolidine-2-carboxylic acid benzyl ester

L-Proline benzyl ester hydrochloride (500 mg, 2.073 mmol) was dissolvedin CH₂Cl₂ (10 ml). Triethylamine (600 mg, 6.0 mmol) andisopropylisocyanate (210 mg, 2.48 mmol) were added. After 18 h at roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (100 ml). This solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 3% methanol,97% chloroform) to give a colourless oil identified as the titlecompound (528 mg, 1.82 mmol, 88%).

B. (2S)-1-(Isopropylcarbamoyl)pyrrolidine-2-carboxylic acid(2S)-1-(Isopropylcarbamoyl)pyrrolidine-2-carboxylic acid benzyl ester(528 mg, 1.82 mmol) was dissolved in THF/H₂O (9:1, 10 ml). Lithiumhydroxide monohydrate (229 mg, 5.46 mmol) was added. After 18 h at roomtemperature the reaction mixture was diluted with ethyl acetate (50 ml).This solution was washed with 1M KHSO₄, water and brine, dried (Na₂SO₄)and evaporated in vacuo to give a colourless oil identified as the titlecompound (148 mg, 0.74 mmol, 41%). C.1-((2′S)-1′-(Isopropylcarbamoyl)pyrrolidine-2′-carbonyl)pyrrolidine

1-((2S)-1-(Isopropylcarbamoyl)pyrrolidine-2-carboxylic acid (25 mg,0.125 mmol) was dissolved in CH₂Cl₂ (10 ml). To this solution was addedpyrrolidine (7 mg, 0.138 mmol), HBTU (52 mg, 0.138 mmol) anddiisopropylethylamine (32.3 mg, 0.323 mmol). After 18 h at 0° C. to roomtemperature the solvent was removed in vacuo and the residue was takenup in ethyl acetate (70 ml). The solution was washed with 0.3M KHSO₄,sat. NaHCO₃, water and brine, dried (Na₂SO₄) and evaporated in vacuo.The residue was purified by flash chromatography (eluant: 1%triethylamine, 2% methanol, 97% chloroform) to give an amber oilidentified as the title compound (11 mg, 0.043 mmol, 35%).

EXAMPLE E29(2R)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylbutanoyl)pyrrolidine-2-boronicacid A.(2R)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylbutanoyl)pyrrolidine-2-boronate-(1S,2S,3R,5S)-pinanediolester

(2R)-1-((2S)-2-(1,1-Dimethylethoxycarbonylamino)-3-methylbutanoyl)pyrrolidine-2-boronate-(1S,2S,3R,5S)-pinanediolester (synthesised as described in WO 0310127) (70 mg, 0.16 mmol) wasdissolved in 4M HCl/dioxin (30 ml). After 1 h at room temperature thesolvent was removed in vacuo and the residue dissolved in CH₂Cl₂ (25ml). The solution was cooled to 0° C., triethylamine (36 mg, 0.36 mmol)was added followed by 2-anisoyl chloride (30 mg, 0.18 mmol). After 18 hat 0° C. to room temperature the solvent was removed in vacuo and theresidue dissolved in ethyl acetate (70 ml). This solution was washedwith 0.3M KHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) andevaporated in vacuo. The residue was purified by flash chromatography(eluant: 60% Pet. ether, 40% ethyl acetate) to give a colourless oilidentified as the title compound (65 mg, 0.13 mmol, 83%).

B.(2R)-1-((2′S)-2′-(2-Methoxybenzoylamino)-3′-methylbutanoyl)pyrrolidine-2-boronicacid

(2R)-1-((2S)-2-(2-Methoxybenzoylamino)-3-methylbutanoyl)pyrrolidine-2-boronate-(1S,2S,3R,5S)-pinanediolester (70 mg, 0.16 mmol) was dissolved in acetone (10 ml). Sodium iodide(106 mg, 0.71 mmol) and 0.1M ammonium acetate (5 ml) were added. After18 h at room temperature the acetone was removed in vacuo and 2M sodiumhydroxide (10 ml) was added to the residue which was washed with CH₂Cl₂.The aqueous layer was acidified to pH 7 with 1M HCl and extracted withchloroform (3×50 ml). The combined organic extracts were washed withwater and brine, dried (Na₂SO₄) and evaporated in vacuo to give acolourless oil identified as the title compound (28 mg, 0.08 mmol, 66%).

EXAMPLE E30(2R)-1-((2′S)-2′-(Ethylcarbamoylamino)-3′-methylbutanoyl)pyrrolidine-2-boronicacid A.(2R)-1-((2′S)-2′-(Ethylcarbamoylamino)-3′-methylbutanoyl)pyrrolidine-2-boronate-(1S,2S,3R,5S)-pinanediolester

(2R)-1-((2S)-2-(1,1-Dimethylethoxycarbonylamino)-3-methylbutanoyl)pyrrolidine-2-boronate-(1S,2S,3R,5S)-pinanediolester (synthesised as described in WO 0310127) (70 mg, 0.16 mmol) wasdissolved in 4M HCl/dioxin (30 ml). After 1 h at room temperature thesolvent was removed in vacuo and the residue dissolved in CH₂Cl₂ (25ml). The solution was cooled to 0° C., triethylamine (36 mg, 0.36 mmol)was added followed by ethylisocyanate (15 mg, 0.21 mmol). After 18 h at0° C. to room temperature the solvent was removed in vacuo and theresidue dissolved in ethyl acetate (70 ml). This solution was washedwith 0.3M KHSO₄, sat. NaHCO₃, water and brine, dried (Na₂SO₄) andevaporated in vacuo. The residue was purified by flash chromatography(eluant: 10% Pet. ether, 90% ethyl acetate) to give a colourless oilidentified as the title compound (48 mg, 0.11 mmol, 73%).

B.(2R)-1-((2′S)-2′-(Ethylcarbamoylamino)-3′-methylbutanoyl)pyrrolidine-2-boronicacid

(2R)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylbutanoyl)pyrrolidine-2-boronate-(1S,2S,3R,5S)-pinanediolester (43 mg, 0.10 mmol) was dissolved in acetone (10 ml). Sodium iodide(87 mg, 0.40 mmol) and 0.1M ammonium acetate (5 ml) were added. After 18h at room temperature the acetone was removed in vacuo and 2M sodiumhydroxide (10 ml) was added to the residue which was washed with CH₂Cl₂.The aqueous layer was acidified to pH 7 with 1M HCl and extracted withchloroform (3×50 ml). The combined organic extracts were washed withwater and brine, dried (Na₂SO₄) and evaporated in vacuo to give acolourless oil identified as the title compound (9 mg, 0.032 mmol, 20%).

EXAMPLE E31(2S)-2-Formyl-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidideA.(2S)-1-((2′S)-2′-(tert-Butyloxycarbonylamino)-3′-methylpentanoyl)-2-hydroxymethylpyrrolidine

N^(α)-(tert-Butyloxycarbonyl)-L-isoleucine (5.0 g, 21.6 mmol) wasdissolved in CH₂Cl₂/DMF (9:1, 100 ml). The solution was cooled to 0° C.,(S)-(+)-2-pyrrolidinemethanol (2.5 g, 24.7 mmol), 1-hydroxybenzotriazolehydrate (5.9 g, 43.7 mmol) and water soluble carbodiimide (5.2 g, 26.0mmol) were added and after 15 min the pH adjusted to pH9 withtriethylamine. After 18 h at 0° C. to room temperature the solvent wasremoved in vacuo and the residue was taken up in ethyl acetate (300 ml).This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water and brine,dried (Na₂SO₄) and evaporated in vacuo. The residue was purified byflash chromatography (eluant: 30% Pet. ether, 70% ethyl acetate) to givea colourless oil identified as the title compound (6.8 g, 21.6 mmol,100%).

B.(2S)-2-Hydroxymethyl-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidide

(2S)-1-((2S)-2-(tert-Butyloxycarbonylamino)-3-methylpentanoyl)-2-hydroxymethylpyrrolidine(2.0 g, 6.36 mmol) was treated with 4M HCl/dioxan (50 ml). After 1 h atroom temperature the solvent was removed in vacuo and the residuedissolved in CH₂Cl₂ (100 ml). The solution was cooled to 0° C.,triethylamine (1.4 g, 14 mmol) was added followed by 2-anisoyl chloride(1.2 g, 7.04 mmol). After 18 h at 0° C. to room temperature the solventwas removed in vacuo and the residue dissolved in ethyl acetate (200ml). This solution was washed with 0.3M KHSO₄, sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 10% Pet. ether, 90% ethyl acetate) togive a colourless oil identified as the title compound (1.53 g, 4.46mmol, 91%).

C.(2S)-2-Formyl-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidide

(2S)-2-Hydroxymethyl-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide(1.3 g, 3.73 mmol) was dissolved in CH₂Cl₂ (100 ml). Dess MartinPeriodinane (2.0 g, 4.8 mmol) was added. After 3 h at room temperaturethe solvent was removed in vacuo and the residue dissolved in ethylacetate (200 ml), washed with sat. NaHCO₃, water and brine, dried(Na₂SO₄) and evaporated in vacuo. The residue was purified by flashchromatography (eluant: 30% Pet. ether, 70% ethyl acetate) to give acolourless oil identified as the title compound (1.05 g, 3.0 mmol, 80%).

EXAMPLE E32(2S)-2-Acetyl-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidideA.(2S)-2-(1-(1R,S)-Hydroxyethyl)-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidide

(2S)-2-Formyl-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide(100 mg, 0.28 mmol) was dissolved in dry THF (30 ml). Methyl magnesiumbromide (1.4M solution in THF/toluene, 4:1, 0.3 ml, 0.42 mmol) was addedto this solution at 0° C. After 4 h at 0° C. to room temperature 0.3MKHSO₄ (20 ml) was added and the reaction mixture extracted with ethylacetate. The organic extract was washed with water and brine, dried(Na₂SO₄) and evaporated in vacuo. The residue was purified by flashchromatography (eluant: 40% Pet. ether, 60% ethyl acetate) to give acolourless oil identified as the title compound (36 mg, 0.099 mmol,35%).

B.(2S)-2-Acetyl-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidide

(2S)-2-(1-(1R,S)-Hydroxyethyl)-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide(32 mg, 0.088 mmol) was dissolved in CH₂Cl₂ (100 ml). Dess MartinPeriodinane (42 mg, 0.099 mmol) was added. After 3 h at room temperaturethe solvent was removed in vacuo and the residue dissolved in ethylacetate (70 ml). This solution was washed with sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 20% Pet. ether, 80% ethyl acetate) togive a colourless oil identified as the title compound (12 mg, 0.033mmol, 38%).

EXAMPLE E33(2S)-2-Propionyl-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidideA.(2S)-2-(1-(1R,S)-Hydroxypropyl)-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidide

(2S)-2-Formyl-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide(150 mg, 0.28 mmol) was dissolved in dry THF (30 ml). Ethyl magnesiumbromide (1M solution in THF, 0.56 ml, 0.56 mmol) was added to thissolution at 0° C. After 18 h at 0° C. to room temperature 0.3M KHSO₄,(20 ml) was added and the reaction mixture extracted with ethyl acetate.The organic extract was washed with water and brine, dried (Na₂SO₄) andevaporated in vacuo. The residue was purified by flash chromatography(eluant: 30% Pet. ether, 70% ethyl acetate) to give a colourless oilidentified as the title compound (62 mg, 0.16 mmol, 38%).

B.(2S)-2-Propionyl-1-((2′S)-2′-(2-methoxybenzoylamino)-3′-methylpentanoyl)pyrrolidide

(2S)-2-(1-(1R,S)-Hydroxypropyl)-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide(52 mg, 0.138 mmol) was dissolved in CH₂Cl₂ (100 ml). Dess MartinPeriodinane (70 mg, 0.17 mmol) was added. After 3 h at room temperaturethe solvent was removed in vacuo and the residue dissolved in ethylacetate (70 ml). This solution was washed with sat. NaHCO₃, water andbrine, dried (Na₂SO₄) and evaporated in vacuo. The residue was purifiedby flash chromatography (eluant: 20% Pet. ether, 80% ethyl acetate) togive a colourless oil identified as the title compound (24 mg, 0.064mmol, 47%).

EXAMPLES E34-E66

Examples E34-E61 were synthesised according to methods described forExamples E1, E2 and E10, while Examples E62-E66 were synthesisedaccording to methods described in Example E31.

Example No Name E34 (2S)-1-(2-(1-Napthoylamino)acetyl)pyrrolidine-2-carbonitrile E35 (2S)-1-((2S)-2-(4- Methylbenzoyl)octahydroindole-2-carbonyl)pyrrolidine-2-carbonitrile E36(2S)-1-((2S)-2-(4-Methoxybenzoylamino)-2-cyclohexylacetyl)pyrrolidine-2-carbonitrile E37(2S)-1-((2S)-1-Benzoylpiperidine-2- carbonyl)pyrrolidine-2-carbonitrileE38 (2S)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylbutanoyl)pyrrolidine-2-carbonitrile E39(2S)-1-((2S)-2-(Pivaloylamino)-3-phenylpropanoyl)pyrrolidine-2-carbonitrile E40(2S)-1-((2S)-2-(N-Cyclohexanoyl-N- methylamino)-3-phenylpropanoyl)pyrrolidine- 2-carbonitrile E41(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3- (methyloxycarbonyl)propanoyl)pyrrolidine-2- carbonitrile E42 (2S)-1-((2S)-2-(4-Chlorobenzoylamino)-4-(benzyloxycarbonyl)butanoyl) pyrrolidine-2- carbonitrile E43(2S)-1-((2S)-2-(4-Methoxybenzoylamino)-5- (benzyloxycarbonylamino)pentanoyl)pyrrolidine- 2-carbonitrile E44(2S)-1-((2S)-2-(3-Methoxybenzoylamino)-6- (benzyloxycarbonylamino)hexanoyl)pyrrolidine- 2-carbonitrile E45(2S)-1-((2S)-2-(Benzoylamino)-3-benzyloxypropanoyl)pyrrolidine-2-carbonitrile E46(2S)-1-((2S)-2-(Cyclohexanoylamino)-2-phenylacetyl)pyrrolidine-2-carbonitrile E47(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-4- (benzyloxycarbonylamino)butanoyl)pyrrolidine- 2-carbonitrile E48(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3- (benzyloxycarbonylamino)propanoyl)pyrrolidine- 2-carbonitrile E49(2S)-1-((2S)-2-(N-Cyclohexanoyl-N- methylamino)-propanoyl)pyrrolidine-2-carbonitrile E50 (2S)-1-((2S)-2-(2-Methoxybenzoylamino)-5-N-(acetylamino)-3,3-dimethyl-4- thiopentanoyl)pyrrolidine-2-carbonitrileE51 (2S)-1-((2S)-2-(N-(2-Methoxybenzoyl)-N-methylamino)-3-methylpentanoyl)pyrrolidine-2- carbonitrile E52(2S)-1-(2-(N-Benzyl-N-(2- methoxybenzoyl)amino)acetyl)pyrrolidine-2-carbonitrile E53 (2S)-1-(2-(2-Methoxybenzoylamino)-2-methylpropanoyl)pyrrolidine-2-carbonitrile E54(2S)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylbutanoyl)pyrrolidine-2-carbonitrile E55 (2S)-1-((2S)-2-(Isopropylcarbamoylamino)propanoyl)pyrrolidine- 2-carbonitrile E56(2S)-1-((2S)-2- (Ethylcarbamoyl)octahydroindole-2-carbonyl)pyrrolidine-2-carbonitrile E57(2S)-1-((2S)-2-(N-Ethylcarbamoyl-N- methylamino)-4-methylpentanoyl)pyrrolidine-2- carbonitrile E58(2S)-1-((2S)-2-(Benzylcarbamoylamino)-3,3-dimethylbutanoyl)pyrrolidine-2-carbonitrile E59(2S)-1-((2S)-2-(Isopropylcarbamoylamino)-3-phenylpropanoyl)pyrrolidine-2-carbonitrile E60(2S)-1-((2S)-2-(Cyclohexylcarbamoylamino)-4-methylpentanoyl)pyrrolidine-2-carbonitrile E61(2S)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylpentanoyl)-3,4-dehydropyrrolidine-2- carbonitrile E62(2S)-2-Formyl-1-((2S)-2-(2- methoxybenzoylamino)-3-methylbutanoyl)pyrrolidine E63 (2S)-2-Formyl-1-((2S)-1-(3-methoxybenzoyl)pyrrolidine-2- carbonyl)pyrrolidine E64(2S)-2-Formyl-1-((2S)-1-(ethylcarbamoyl)octahydroindole-2-carbonyl)pyrrolidine E65 (2S)-2-Formyl-1-((2S)-2-(2-methoxybenzoyl)octahydroindole-2- carbonyl)pyrrolidine E66(2S)-2-Formyl-1-((2S)-2-(2- methoxybenzoylamino)-3-phenylpropanoyl)pyrrolidine

Example MS: No. Structure Mol Wt [M + H]+ E1

342.43 344.2 E2

280.37 281.2 E3

343.43 344.2 E4

343.43 344.2 E5

293.41 294.1 E6

327.39 328.1 E7

278.36 279.2 E8

343.43 344.2 E9

331.80 332.1 E10

343.43 344.2 E11

372.54 373.1 E12

294.42 295.1 E13

343.43 344.2 E14

344.42 344.42 E15

358.44 359.2 E16

361.47 362.1 E17

365.38 366.2 E18

302.33 303.1 E19

300.31 301.1 E20

341.41 342.2 E21

357.46 358.2 E22

329.40 330.2 E23

377.48 378.2 E24

393.47 394.1 E25

318.42 319.1 E26

354.40 355.2 E27

320.41 321.1 E28

253.35 254.2 E29

348.21 349.2 E30

285.15 286.4 E31

346.43 347.2 E32

360.46 361.2 E33

374.48 397.2 (M +Na) E34

307.36 308.1 E35

365.48 366.2 E36

369.47 370.2 E37

311.39 312.2 E38

329.40 330.1 E39

327.43 328.2 E40

367.50 368.1 E41

359.39 360.1 E42

453.93 454.1, 455.3 E43

478.55 479.2 E44

492.58 493.2 E45

377.45 378.1 E46

339.44 340.3 E47

464.53 465.2 E48

450.50 451.3 E49

291.40 292.2 E50

432.55 433.1 E51

257.46 358.15 E52

377.45 378.2 E53

315.38 316.2 E54

266.35 267.2 E55

252.32 253.1 E56

319.42 319.6 E57

294.40 295.2 E58

342.44 343.3 E59

328.42 329.2 E60

331.47 335.2 E61

278.36 279.1 E62

334.40 333.2 E63

330.39 331.3 E64

321.42 322.3 E65

384.48 385.2 E66

380.45 381.3

The ¹H NMR data for Examples E1-E66 are as follows

Example No ¹H NMR: δ(ppm) E1 (CDCl₃): δ 0.982 (3H, t, J = 7.4 Hz), 1.02(3H, d, J = 6.4 Hz), 1.19-1.26 (2H, m), 1.93-1.95 (2H, m), 2.12-2.25(4H, m), 3.72-3.76 (1H, m), 3.97 (3H, s), 4.76-4.80 (2H, m), 6.94-7.02(2H, m), 7.39-7.46 (1H, m), 8.08-8.12 (1H, m), 8.45 (1H, d, J = 7.4 Hz)E2 (CDCl₃): δ 0.86-0.96 (6H, m), 1.07-1.19 (5H, m), 1.59-1.74 (2H, m),2.05-2.27 (4H, m), 3.10-3.22 (3H, m), 3.68-3.74 (1H, m), 3.91-4.00 (1H,m), 4.41 (1H, d, J = 8.9 Hz), 4.65-4.69 (1H, m) E3 (CDCl₃): δ 0.88-1.02(7H, m), 1.1-1.3 (1H, m), 1.63-1.70 (1H, m), 1.9-2.1 (2H, m), 2.2-2.4(3H, m), 3.79 (3H, s), 3.9-4.1 (1H, m), 4.67-4.96 (2H, m), 6.99-7.11(2H, m), 7.26-7.27 (3H, m) E4 (CDCl₃): δ 0.88-0.94 (3H, m), 1.04-1.06(2H, m), 1.1-1.3 (1H, m), 1.55-1.70 (1H, m), 1.90-2.05 (1H, m), 2.1-2.3(3H, m), 3.7-3.8 (1H, m), 3.82 (3H, s), 3.9-4.0 (1H, m), 4.7-4.76 (2H,m), 6.70 (1H, d, J = 8.6 Hz), 6.90 (2H, d, J = 8 Hz), 7.71 (2H, d, J = 8Hz) E5 (CDCl₃): δ 0.87-0.90 (7H, m), 1.2 (9H, s), 1.51-1.60 (1H, s),1.8-1.83 (1H, m), 2.1-2.22 (4H, m), 3.66-3.67 (1H, m), 3.82-3.84 (1H,m), 4.5-4.53 (1H, m), 4.71-4.74 (1H, m), 6.19-6.22 (1H, m) E6 (CDCl₃): δ2.03-2.29 (10H, m), 3.51-3.58 (1H, m), 3.65-3.70 (1H, m), 3.79 (3H, s),4.68-4.73 (1H, m), 4.82-4.86 (1H, m), 6.91-6.96 (1H, m), 7.04-7.11 (1H,m), 7.24-7.30 (2H, m) E7 (CDCl₃): δ 1.11 (6H, d, J = 6.4 Hz), 2.03-2.26(9H, m), 3.25-3.30 (1H, m), 3.42-3.49 (1H, m), 3.58-3.67 (1H, m),3.78-3.89 (2H, m), 4.53-4.56 (1H, m), 4.78-4.82 (1H, m) E8 (CDCl₃): δ1.108 (9H, s), 2.02-2.21 (5H, m), 3.78-3.79 (1H, m), 3.99 (3H, s), 4.77(2H, d, J = 8.9 Hz), 6.95-7.07 (2H, m), 8.116 (1H, d, J = 7.9 Hz), 8.65(1H, d, J = 8.7 Hz) E9 (CDCl₃): δ 1.80-2.50 (7H, m), 3.40-3.60 (1H, m),3.60-3.80 (2H, m), 3.90-4.10 (1H, m), 4.70-4.80 (1H, m), 4.80-4.95 (1H,m), 7.20-7.70 (5H, m) E10 (CDCl₃): δ 0.90-1.10 (6H, m), 1.50-1.80 (3H,m), 2.10-2.40 (4H, m), 3.60-3.75 (1H, m), 3.75-3.90 (4H, m), 4.70-4.80(1H, m), 4.85-5.00 (1H, m), 6.85-6.95 (1H, m), 7.25-7.40 (3H, m) E11(CDCl₃): δ 0.89-0.97 (6H, m), 1.1-1.29 (1H, m), 1.63-1.85 (2H, m),2.1-2.12 (4H, m), 2.83-2.88 (2H, m), 3.60-3.63 (3H, m), 3.8-3.9 (2H, m),4.3-4.4 (1H, m), 4.83-4.89 (1H, m), 6.68-6.90 (1H, m), 7.16-7.26 (5H,m), 7.9-7.7 (1H, m) E12 (CDCl₃): δ 0.91 (3H, t, J = 7 Hz), 1.58 (2H, t,J = 7 Hz), 1.9-2.21 (7H, m), 2.36-2.40 (1H, m), 3.42-3.62 (5H, m),4.04-4.07 (1H, m), 4.81-4.83 (1H, m), 5.06-5.09 (1H, m), 5.50-5.52 (1H,m) E13 (CDCl₃): δ 0.65-0.90 (3H, m), 0.90-1.55 (4H, m), 1.85-2.45 (3H,m), 3.40-4.00 (8H, m), 4.75-5.00 (1H, m), 6.80-7.10 (2H, m), 7.15-7.40(2H, m) E14 (CDCl₃): δ 1.50-2.00 (3H, m) 2.05-2.50 (7H, m), 2.70-2.90(2H, m), 3.85-3.90 (2H, m), 3.99 (3H, s), 4.70-4.80 (1H, m), 4.90-5.10(1H, m), 6.90-7.20 (2H, m), 7.40-7.50 (1H, m), 8.05-8.15 (1H, m), 8.62(1H, d, J = 7.91 Hz) E15 (CDCl₃): δ 1.40-1.70 (4H, m), 1.70-2.10 (5H,m), 2.10-2.40 (3H, m), 2.65-2.80 (2H, m), 3.65-3.95 (2H, m), 4.00 (3H,s), 4.75-4.85 (1H, m), 4.90-5.10 (1H, m), 6.90-7.10 (2H, m), 7.30-7.40(1H, m), 8.05-8.15 (1H, m), 8.60 (1H, d, J = 7.91 Hz) E16 (CDCl₃): δ0.9-0.92 (3H, m), 1.02-1.05 (3H, m), 1.15-1.35 (1H, m), 1.6-1.8 (1H, m),1.9-2.1 (1H, m), 3.24 (2H, s), 3.81 (3H, s), 4.68-4.73 (2H, m), 5.11(1H, d, J = 8 Hz), 5.25 (1H, s), 6.83-6.86 (1H, m), 7.01-7.1 (1H, m),7.27-7.30 (3H, m) E17 (CDCl₃): δ 1.07 (6H, d, J = 6.68 Hz), 2.05-2.30(1H, m), 2.64-2.82 (2H, m), 3.99 (3H, s), 4.00-4.18 (1H, m), 4.38-4.58(2H, m), 5.01 (1H, t, J = 6.44 Hz), 6.82-7.00 (2H, m), 7.46 (1H, t, J =7.67 Hz), 8.10 (1H, d, J = 6.68 Hz), 8.44 (1H, d, J = 7.67 Hz) E18(CDCl₃): δ 0.99 (6H, d, J = 6.43), 1.13 (3H, t, J = 7.42 Hz), 1.85-2.05(1H, m), 2.65-2.85 (2H, m), 3.05-3.30 (3H, m), 3.95-4.10 (1H, m), 4.16(1H, t, J = 8.41 Hz), 4.30-4.50 (1H, m), 4.80-5.00 (2H, m), 5.46 (1H, d,J = 8.41 Hz) E19 (CDCl₃): δ 1.11 (3H, t), 1.90-2.20 (2H, m), 2.20-2.40(1H, m), 2.60-2.80 (2H, m), 3.10-3.35 (4H, m), 3.40-3.55 (1H, m),3.88-4.05 (1H, m), 4.20-4.50 (3H, m), 4.95-5.10 (1H, br, t) E20 (CDCl₃):δ 0.93 (3H, t, J = 7.42 Hz), 1.05 (2H, d, J = 6.68 Hz), 1.12-1.40 (1H,m), 1.60-1.80 (1H, m), 1.90-2.10 (1H, m), 3.98 (3H, s), 4.40-4.55 (1H,m), 4.72 (1H, t, J = 8.41 Hz), 4.82-4.96 (1H, m), 5.35-5.45 (1H, m),5.80-5.90 (1H, m), 6.05-6.18 (1H, m), 6.90-7.10 (2H, m), 7.44 (1H, t, J= 7.05 Hz), 8.11 (1H, d, J = 6.43, J = 6.43 Hz), 8.45 (1H, d, J = 8.16Hz) E21 (CDCl₃): δ 0.87-0.92 (8H, m), 1.2-1.3 (1H, m), 1.4-2.0 (6H, m),3.28-3.39 (1H, m), 3.99 (3H, s), 4.1-4.16 (1H, m), 5.09-5.15 (1H, m),5.75-5.86 (1H, m), 6.95 (1H, d, J = 8 Hz), 7.1 (1H, m), 7.44 (1H, m),8.12 (1H, m), 8.44-8.50 (1H, m) E22 (CDCl₃): δ 0.85-1.05 (6H, m),1.02-1.40 (1H, m), 1.55-1.75 (1H, m), 1.80-2.00 (1H, m), 2.55-2.80 (1H,m), 3.00-3.15 (1H, m), 3.97 (3H, s), 4.28-4.55 (3H, m), 4.80-4.95 (1H,m), 6.90-7.10 (2H, m), 7.44 (1H, J = 7.67 Hz), 8.12 (1H, d, J = 7.67Hz), 8.40 (1H, d, J = 7.42 Hz) E23 (CDCl₃): δ 0.89-1.02 (7H, m), 1.2-1.3(1H, m), 1.61-1.63 (1H, m), 2.01-2.07 (1H, m), 3.12-3.18 (1H, m),3.56-3.58 (1H, m), 3.80 (3H, s), 4.26-4.31 (1H, m), 4.78-4.82 (1H, m),5.64-5.73 (2H, m), 6.99-7.00 (2H, m), 7.24-7.28 (4H, m) E24 (CDCl₃): δ0.89-1.02 (7H, m), 1.2-1.3 (1H, m), 1.61-1.63 (1H, m), 2.01-2.07 (1H,m), 3.58-3.60 (2H, m), 3.81 (3H, s), 4.74-4.61 (2H, m), 5.64-5.58 (2H,m), 6.91-7.00 (1H, m), 7.10-7.20 (1H, m), 7.24-7.28 (4H, m) E25 (CDCl₃):δ 0.80-1.05 (6H, m), 1.05-2.05 (6H, m), 3.00-3.15 (1H, m), 3.35-3.60(3H, m), 3.68-3.90 (1H, m), 3.98 (3H, s), 4.80-4.95 (1H, m), 6.90-7.10(2H, m), 7.35-7.45 (1H, t), 8.10-8.20 (1H, d), 8.45-8.65 (1H, m) E28(CDCl₃): δ 1.05-1.25 (6H, d), 1.70-2.40 (9H, m), 3.20-4.20 (7H, m),4.55-4.70 (1H, m) E29 (CDCl₃): δ 0.84-0.92 (8H, m), 1.91-2.05 (5H, m),2.96-2.99 (1H, m), 3.46-3.52 (1H, m), 3.81-3.92 (1H, m), 3.96 (3H, s),4.75-4.82 (1H, m), 6.93-7.06 (2H, m), 7.39-7.42 (1H, m), 8.10-8.14 (1H,m), 8.34-8.38 (1H, m) E30 (CDCl₃): δ 0.83-1.27 (9H, m), 1.99-2.16 (5H,m), 3.10-3.20 (1H, m), 3.42-3.47 (2H, m), 3.50-3.65 (2H, m), 4.10 (1H,d), 5.28 (1H, s) E31 (CDCl₃): δ 0.81-0.92 (3H, m), 1.02-1.05 (3H, m),1.10-1.30 (1H, m), 1.55-1.75 (1H, m), 1.86-2.20 (6H, m), 3.65-3.68 (1H,m), 3.92 (3H, s), 4.47-4.50 (1H, m), 4.85-4.88 (1H, m), 6.91-7.03 (2H,m), 7.30-7.45 (1H, m), 8.09-8.11 (1H, d), 8.43-8.46 (1H, d), 9.51 (1H,s) E32 (CDCl₃): δ 0.86-0.91 (6H, m), 1.05-1.09 (3H, m), 1.21-1.26 (2H,m), 1.55-1.65 (1H, m), 1.85-1.93 (2H, m), 2.21 (3H, s), 3.67-3.71 (1H,m), 3.96 (3H, s), 4.08-4.11 (1H, m), 4.57-4.63 (1H, m), 4.85-4.91 (1H,m), 6.95 (1H, d, J = 8.4 Hz), 7.01-7.06 (1H, m), 8.13 (1H, d, J = 7.2Hz), 8.46 (1H, d) E33 (CDCl₃): δ 0.92-1.00 (6H, m), 1.06-1.09 (3H, m),1.18-1.23 (2H, m), 1.62-2.13 (6H, m), 2.52-2.59 (2H, m), 3.68-3.72 (1H,m), 3.95 (3H, s), 4.58-4.63 (1H, m), 4.84-4.90 (1H, m), 6.93-6.96 (1H,m), 7.01-7.06 (1H, m), 7.39-7.44 (1H, m), 8.14 (1H, d, J = 6.7 Hz)8.40-8.44 (1H, m) E34 (CDCl₃): 2.10-2.40 (4H, m), 3.45-3.80 (2H, m),4.20-4.50 (2H, m), 4.80-4.90 (1H, m), 6.90-7.10 (1H, m), 7.40-7.70 (4H,m), 7.80-8.00 (2H, m), 8.45 (1H, d, J = 7.42 Hz) E35 (CDCl₃): 0.80-1.10(1H, m), 1.20-1.80 (6H, m), 1.80-2.50 (10H, m), 3.50-3.70 (2H, m),4.00-4.15 (1H, m), 4.65-4.75 (1H, m), 4.80-4.95 (1H, m), 7.10-7.40 (5H,m) E36 (CDCl₃): 1.00-1.40 (5H, m), 1.50-1.90 (7H, m), 2.10-2.40 (3H, m),3.60-4.00 (5H, m), 4.70-4.80 (2H, m), 6.57 (1H, d, J = 8.40 Hz), 6.90(2H, d, J = 8.64 Hz), 7.73 (2H, d, J = 8.64 Hz) E37 (CDCl₃): 1.35-1.90(5H, m), 1.95-2.40 (5H, m), 3.50-3.90 (4H, m), 4.75-4.85 (1H, m),5.30-5.45 (1H, m), 7.30-8.20 (5H, m) E38 (CDCl₃): 0.90-1.10 (6H, m),1.40-1.60 (1H, m), 2.10-2.40 (4H, m), 3.70-4.00 (5H, m), 4.70-4.85 (2H,m), 6.70-6.85 (1H, m), 6.95-7.10 (1H, m), 7.20-7.40 (3H, m) E39 (CDCl₃):1.11 (9H, s), 1.70-2.15 (4H, m), 2.55-2.65 (1H, m), 2.95-3.05 (2H, m),3.30-3.45 (1H, m) 4.60-4.80 (2H, m), 6.35-6.45 (1H, m), 7.20-7.40 (5H,m) E40 (CDCl₃): 1.00-2.50 (12H, m), 2.85-3.10 (1H, m), 3.14 (3H, s),3.40-3.60 (2H, m), 4.55-4.70 (1H, m), 5.35-5.50 (1H, m), 7.10-7.50 (5H,m) E41 (CDCl₃): 1.10-1.30 (1H, m) 2.00-2.40 (4H, m), 2.75-2.95 (2H, m),3.72 (3H, s), 3.80-3.95 (1H, m), 3.98 (3H, s), 4.70-4.80 (1H, m),5.25-5.40 (1H, m), 6.97 (1H, d, J = 8.42 Hz), 7.05 (1H, t, J = 7.67 Hz),7.46 (1H, t, J = 7.67 Hz), 8.14 (1H, d, J = 7.91 Hz), 8.83 (1H, d, J =8.15 Hz) E42 (CDCl₃): 1.80-2.30 (4H, m) 2.45-2.90 (2H, m), 3.10-3.30(1H, m), 3.60-4.10 (3H, m), 4.70-5.20 (4H, m), 7.20-7.50 (7H, m),7.60-7.80 (3H, m) E43 (CDCl₃): 1.20-1.40 (1H, m), 1.50-1.90 (4H, m),2.00-2.40 (4H, m), 3.20-3.30 (2H, m), 3.60-3.90 (5H, m), 4.75-4.85 (1H,m), 4.85-4.95 (1H, m), 5.07 (2H, s), 6.88 (2H, d, J = 8.66 Hz),7.00-7.10 (1H, m), 7.20-7.50 (5H, m), 7.74 (2H, d, J = 8.66 Hz) E44(CDCl₃): 1.40-1.70 (5H, m), 1.70-2.00 (1H, m), 2.10-2.40 (4H, m)3.10-3.40 (2H, m) 3.60-3.90 (5H, m), 4.70-4.90 (3H, m), 5.00-5.20 (2H,m), 6.90-7.10 (2H, m), 7.20-7.50 (8H, m) E45 (CDCl₃): 1.90-2.40 (4H, m),3.50-3.90 (4H, m), 4.40-4.80 (4H, m), 5.05-5.30 (1H, m), 6.95-7.15 (1H,m), 7.20-7.60 (8H, m), 7.70-7.90 (2H, m) E46 (CDCl₃): 1.00-1.50 (6H, m)1.60-2.40 (9H, m), 2.95-3.20 (1H, m), 3.65-3.85 (1H, m), 4.67 (1H, d, J= 6.67 Hz), 5.67 (1H, d, J = 7.15 Hz) 6.90-7.10 (1H, m), 7.20-7.60 (5H,m) E47 (CDCl₃): 1.33 (1H, t J = 7 Hz), 1.70-1.71 (1H, m), 1.95-2.30 (4H,m), 2.96-3.11 (1H, m), 3.46-3.51 (3H, m), 3.98 (3H, s), 4.72-4.73 (1H,m), 4.9-5.3 (3H, m), 6.03-6.07 (1H, m), 6.9-7.1 (2H, m), 7.3-7.5 (6H,m), 8.08-8.1 (1H, m), 8.86-8.89 (1H, m) E48 (CDCl₃): 2.11-2.24 (4H, m),3.57-3.6 (1H, m), 3.65-3.83 (2H, m), 3.92 (3H, s), 4.73-4.74 (1H, m),5.07-5.11 (3H, m), 5.49 (1H, m), 6.9-7.1 (2H, m), 7.25-7.32 (7H, m),8.11-8.14 (1H, m), 8.81-8.4 (1H, m) E49 (CDCl₃): 1.10-1.50 (10H, m),1.60-2.00 (4H, m), 2.00-2.40 (3H, m), 2.85-3.05 (3H, m) 3.50-3.80 (5H,m) E50 (CDCl₃): 1.50 (6H, d, J = 7.67 Hz), 1.94 (3H, s), 2.10-2.40 (4H,m), 3.70-4.20 (7H, m), 4.65-4.80 (2H, m), 4.94 (1H, d, J = 8.15 Hz),6.90-7.20 (3H, m), 7.20-7.60 (1H, m), 8.05-8.25 (1H, m) E51 (CDCl₃):0.80-1.05 (8H, m), 1.05-1.30 (1H, m), 2.00-2.40 (6H, m), 2.70-3.00 (1H,m), 3.60-3.90 (5H, m), 4.65-4.80 (1H, m), 5.10-5.30 (1H, m), 6.80-7.05(2H, m), 7.10-7.40 (2H, m) E52 (CD₃OD): 1.80-2.45 (6H, m), 3.79 (2H, s),3.89 (3H, s), 4.78 (1H, br, t), 4.87 (2H, s), 6.95-7.25 (2H, m),7.25-7.60 (7H, m) E54 (CDCl₃): 0.70-1.20 (10H, m), 1.80-2.00 (1H, m),2.05-2.35 (5H, m), 3.05-3.30 (2H, m), 3.60-3.80 (1H, m), 3.85-4.00 (1H,m), 4.30-4.50 (1H, m), 4.60-4.75 (1H, m) E55 (CDCl₃): 1.00-1.20 (9H, m),1.20-1.40 (3H, m), 2.10-2.40 (3H, m), 3.70-3.90 (2H, m), 4.60-4.80 (2H,m), 5.59 (1H, d, J = 8.81 Hz E56 (CDCl₃): 1.00-1.20 (6H, m), 1.20-1.55(1H, m), 1.55-2.50 (10H, m), 3.10-3.35 (3H, m), 3.35-3.65 (2H, m),3.85-4.00 (1H, m), 4.05-4.20 (1H, m), 4.60-4.80 (1H, m), 5.80-5.90 (1H,m E57 (CDCl₃): 0.80-0.95 (6H, m), 0.95-1.20 (5H, m), 1.95-2.30 (5H, m),2.89 (3H, s), 3.15-3.40 (2H, m), 3.65-3.80 (1H, m), 3.90-4.10 (1H, m),4.35-4.55 (1H, m), 4.60-4.70 (1H, m), 4.85 (1H, d, J = 11.12 Hz) E58(CDCl₃): 0.99 (9H, s), 1.80-2.15 (3H, m), 3.60-3.72 (1H, m), 3.72-3.86(1H, m), 4.05-4.15 (1H, m), 4.22-4.60 (4H, m), 5.68-5.85 (2H, m),7.15-7.35 (5H, m). E59 (CDCl₃): 0.90-1.50 (6H, m), 1.50-2.10 (4H, m),2.50-2.70 (1H, m), 2.90-3.20 (3H, m), 3.40-3.55 (1H, m), 3.75-3.90 (1H,m), 4.60-4.80 (2H, m), 5.60-5.80 (1H, m), 7.15-7.40 (5H, m) E60 (CDCl₃):0.80-2.00 (19H, m), 2.05-2.40 (4H, m), 3.35-3.50 (1H, m), 3.55-3.70 (1H,m), 3.80-3.95 (1H, m), 4.50-4.80 (3H, m), 5.48 (1H, d, J = 8.67 Hz) E61(CDCl₃): 0.90 (3H, t, J = 7.42 Hz), 0.97 (3H, d, J = 6.68 Hz), 1.10 (3H,t, J = 7.30 Hz), 1.58-1.88 (2H, m), 3.05-3.35 (2H, m), 4.30-4.52 (2H,m), 4.80-5.00 (1H, m), 5.10-5.25 (1H, m), 5.30-5.40 (1H, m), 5.75-5.90(1H, m), 5.90-6.05 (1H, m), 6.05-6.20 (1H, m) E63 (CDCl₃) 1.64-2.40 (8H,m), 3.45-3.90 (7H, m), 4.60-4.70 (1H, m), 4.80-4.90 (1H, m), 6.85-7.00(1H, m), 7.00-7.18 (2H, m), 7.20-7.35 (1H, m), 9.54 (1H, s) E64 (CDCl₃)0.80-1.50 (6H, m), 1.60-2.20 (13H, m), 3.10-3.30 (2H, m), 3.40-3.60 (2H,m), 3.80-4.20 (1H, m), 4.50-4.70 (2H, m), 9.53 (1H, s) E65 (CDCl₃)1.00-1.70 (8H, m), 1.80-2.40 (6H, m), 3.20-3.50 (3H, m), 3.72 (3H, s),3.80-4.00 (1H, m), 4.20-4.60 (1H, m), 4.60-4.80 (1H, m), 6.70-6.85 (2H,m), 6.90-7.20 (1H, m), 7.50-7.90 (1H, m), 9.43 (1H, s)

EXAMPLES

TABLE 1

Example No. R X Mol Wt [M + H]+ 1 CH₃ CH₂ 251.33 252.39 2 S 269.367270.37 3 CH₂CH₂ 265.357 266.37 4 CF₂ 287.31 288.47 5 6 7 8

CH₂ S CH₂CH₂ CF₂ 313.401 331.438 327.428 349.381 314.39 332.18 328.35350.44 9 10 11 12

CH₂ S CH₂CH₂ CF₂ 347.846 365.883 361.873 383.826 348.32 366.17 362.29384.42 13 14 15 16

CH₂ S CH₂CH₂ CF₂ 347.846 365.883 361.873 383.826 348.39 366.1 362.28384.45 17 18 19 20

CH₂ S CH₂CH₂ CF₂ 347.846 365.883 361.873 383.826 348.37 366.11 362.32384.46 21 22 23 24

CH₂ S CH₂CH₂ CF₂ 382.291 400.328 396.318 418.271 382.35 400.09 396.23418.36 25 26 27 28

CH₂ S CH₂CH₂ CF₂ 382.291 400.328 396.318 418.271 382.36 400.1 396.26418.29 29 30 31

CH₂ S CH₂CH₂ 382.291 400.328 396.318 382.33 400.16 396.27 32 33 34 35

CH₂ S CH₂CH₂ CF₂ 331.391 349.428 345.418 367.371 332.34 350.16 346.29368.45 36 37 38 39

CH₂ S CH₂CH₂ CF₂ 331.391 349.428 345.418 367.371 332.35 350.15 346.35368.44 40 41 42

S CH₂CH₂ CF₂ 361.464 357.454 379.407 362.17 358.3 380.48 43 44

CH₂CH₂ CF₂ 357.454 379.407 358.38 380.51 45

CF₂ 393.39 394.54 46 47 48 49

CH₂ S CH₂CH₂ CF₂ 327.428 345.465 341.455 363.408 328.4 346.16 342.37364.41 50 51 52 53

CH₂ S CH₂CH₂ CF₂ 327.428 345.465 341.455 363.408 328.43 346.17 342.33364.44 54 55 56 57

CH₂ S CH₂CH₂ CF₂ 327.428 345.465 341.455 363.408 328.42 346.21 342.33364.46 58 59 60 61

CH₂ S CH₂CH₂ CF₂ 381.398 399.435 395.425 417.378 382.38 400.15 396.33418.4 62 63 64

CH₂ S CF₂ 358.398 376.435 394.378 359.38 377.22 395.61 65 66 67 68

CH₂ S CH₂CH₂ CF₂ 363.461 381.498 377.488 399.441 364.42 382.24 378.37400.49 69 70 71 72

CH₂ S CH₂CH₂ CF₂ 363.461 381.498 377.488 399.441 364.41 382.19 378.36400.46 73 74 75 76

CH₂ S CH₂CH₂ CF₂ 369.509 387.546 383.536 405.489 370.48 388.24 384.39406.47 77

CH₂ 389.499 391.45 78 79 80 81

CH₂ S CH₂CH₂ CF₂ 331.391 349.428 345.418 367.371 332.39 350.18 346.38368.45 82 83 84 85

CH₂ S CH₂CH₂ CF₂ 382.291 400.328 396.318 418.271 382.31 400.1 396.25418.32 86 87 88

CH₂ S CH₂CH₂ 381.398 399.435 395.425 382.4 400.06 396.32 89 90 91

CH₂ S CF₂ 392.302 410.339 428.282 392.34 410.05 428.28 92

S 361.464 362.16 93 94 95 96

CH₂ S CH₂CH₂ CF₂ 385.508 403.545 399.535 421.488 386.47 404.24 400.43422.46 97 98 99 100

CH₂ S CH₂CH₂ CF₂ 387.48 405.417 401.507 423.46 388.47 406.2 402.37424.41 101 102 103 104

CH₂ S CH₂CH₂ CF₂ 397.563 415.6 411.59 433.543 398.47 416.25 412.41434.45 105 106 107 108

CH₂ S CH₂CH₂ CF₂ 327.428 345.465 341.455 363.408 328.41 346.19 342.35364.52 109 110 111

CH₂ CH₂CH₂ CF₂ 341.455 355.482 377.435 342.43 356.35 378.58 112 113

CH₂ CF₂ 369.487 405.467 370.38 406.37 114 115 116 117

CH₂ S CH₂CH₂ CF₂ 319.427 337.464 333.454 355.407 320.33 338.15 334.3356.33 118 119 120 121

CH₂ S CH₂CH₂ CF₂ 303.262 321.399 317.389 339.342 304.32 322.14 318.35340.39 122 123 124

CH₂ S CH₂CH₂ 348.834 366.871 362.861 349.34 367.28 363.33 125 126 127128

CH₂ S CH₂CH₂ CF₂ 357.454 375.491 371.481 393.434 358.42 376.24 372.35394.43 129 130 131 132

CH₂ S CH₂CH₂ CF₂ 319.449 337.486 333.476 355.429 320.43 338.2 334.34356.5 133 134 135

CH₂ S CF₂ 305.422 323.459 341.402 306.46 324.15 342.46 136 137 138 139

CH₂ S CH₂CH₂ CF₂ 291.395 309.432 305.422 327.375 292.4 310.19 306.35328.42 140 141 142

CH₂ S CF₂ 277.368 295.405 313.348 278.38 296.15 314.45 143 144 145 146

CH₂ S CH₂CH₂ CF₂ 319.449 337.486 333.476 355.429 320.44 338.2 334.39356.47 147 148

S CF₂ 344.448 329.391 311.91 330.46 149 150 151 152

CH₂ S CH₂CH₂ CF₂ 307.438 325.475 321.465 343.418 308.46 326.21 322.4344.48 153 154

CH₂ CF₂ 307.438 343.418 308.41 344.49 155 156 157 158

CH₂ S CH₂CH₂ CF₂ 335.492 353.529 349.519 371.472 336.46 354.26 350.39372.61 159 160

CH₂ S 323.393 341.43 324.4 342.17 161 162 163

CH₂ S CF₂ 379.501 397.538 415.481 380.48 398.24 416.48 164 165 166 167

CH₂ S CH₂CH₂ CF₂ 353.466 371.503 367.493 389.446 354.42 372.22 368.37390.51 168 169 170 171

CH₂ S CH₂CH₂ CF₂ 397.397 415.434 411.424 433.377 398.39 416.21 412.33434.44 172 173 174 175

CH₂ S CH₂CH₂ CF₂ 349.381 367.418 363.408 385.361 350.36 368.1 364.31386.47 173 177 178

CH₂ S CF₂ 356.47 374.507 392.45 357.45 375.21 393.52 179 180 181 182

CH₂ S CH₂CH₂ CF₂ 314.389 332.426 328.416 350.369 315.38 333.17 329.32351.42 183 184 185

S CH₂CH₂ CF₂ 332.426 328.416 350.369 333.17 329.32 351.44 186 187 188189

CH₂ S CH₂CH₂ CF₂ 371.525 389.562 385.552 407.505 372.46 390.25 386.44408.49 190 191

CH₂S 367.371 385.408 368.35 386.01 192 193 194 195

CH₂ S CH₂CH₂ CF₂ 333.454 351.491 347.481 369.434 334.38 352.14 348.31370.44 196 197 198 199

CH₂ S CH₂CH₂ CF₂ 343.427 361.464 357.454 379.407 344.41 362.14 358.33380.48 200 201 202

CH₂ S CH₂CH₂ 349.381 367.418 363.408 350.4 368.12 364.34 203 204 205 206

CH₂ S CH₂CH₂ CF₂ 355.482 373.519 369.509 391.462 356.4 374.18 370.39392.49 207 208 209 210

CH₂ S CH₂CH₂ CF₂ 319.427 337.464 333.454 355.407 320.31 338.1 334.28356.36 211 212

CH₂ S 349.381 367.418 350.4 368.2 213

CF₂ 405.467 406.38 214 215

CH₂ S 349.381 367.418 350.38 368.09

TABLE 2

Example No. R X′ Mol Wt [M + H]+ 216 CH₃ CH₂ 237.303 238.36 217 218

CH₂ —CH═CH— 299.374 311.385 300.36 312.12 219 220

CH₂ —CH═CH— 333.819 345.83 334.33 346.16 21 222

CH₂ —CH═CH— 333.819 345.83 334.35 346.11 223 224

CH₂ —CH═CH— 333.819 345.83 334.38 346.12 225 226

CH₂ —CH═CH— 368.264 380.275 368.38 380.09 227 228

CH₂ —CH═CH— 368.264 380.275 368.3 380.11 229 230

CH₂ —CH═CH— 368.264 380.275 368.36 380.08 231 232

CH₂ —CH═CH— 317.364 329.375 318.38 330.17 233 234

CH₂ —CH═CH— 317.364 329.375 318.4 330.15 235 236

CH₂ —CH═CH— 329.4 341.411 330.39 342.16 237 238

CH₂ —CH═CH— 329.4 341.411 330.42 342.16 239 240

CH₂ —CH═CH— 313.401 325.412 314.41 326.2 241 242

CH₂ —CH═CH— 313.401 325.412 314.38 326.21 243 244

CH₂ —CH═CH— 313.401 325.412 314.43 326.26 245 246

CH₂ —CH═CH— 324.384 336.395 325.34 337.23 247 248

CH₂ —CH═CH— 367.382 379.382 368.39 380.17 249 250

CH₂ —CH═CH— 344.371 356.382 345.43 357.13 251

—CH═CH— 336.395 336.09 252 253

CH₂ —CH═CH— 349.434 361.445 350.44 362.17 254 255

CH₂ —CH═CH— 349.434 361.445 350.43 362.18 256 257

CH₂ —CH═CH— 355.482 367.493 356.43 368.23 258

—CH═CH— 387.483 389.19 259 260

CH₂ —CH═CH— 317.364 329.375 318.37 330.2 261 262

CH₂ —CH═CH— 368.264 380.275 368.34 380.07 263 264

CH₂ —CH═CH— 367.371 379.382 368.41 380.19 265 266

CH₂ —CH═CH— 378.275 390.286 378.35 390.07 267 268

CH₂ —CH═CH— 371.481 383.492 372.46 384.25 269 270

CH₂ —CH═CH— 373.453 385.464 374.44 386.21 271 272

CH₂ —CH═CH— 383.536 395.547 384.51 396.26 273 274

CH₂ —CH═CH— 313.401 325.412 314.45 326.22 275 276

CH₂ —CH═CH— 327.428 339.439 328.45 340.19 277 278

CH₂ —CH═CH— 305.4 317.411 306.34 318.04 279 280

CH₂ —CH═CH— 289.335 301.346 290.39 302.12 281 282

CH₂ —CH═CH— 334.807 346.818 335.5 347.19 283 284

CH₂ —CH═CH— 343.427 355.438 344.43 356.21 285 286

CH₂ —CH═CH— 305.422 317.433 306.44 318.2 287 288

CH₂ —CH═CH— 291.395 303.406 22.42 304.13 289 290

CH₂ —CH═CH— 277.368 289.379 278.43 290.12 291 292

CH₂ —CH═CH— 263.341 275.352 364.46 276.08 293 294

CH₂ —CH═CH— 305.422 317.433 306.41 318.25 295 296

CH₂ —CH═CH— 279.384 291.395 280.48 292.16 297 298

CH₂ —CH═CH— 293.411 305.422 294.45 306.19 299 300

CH₂ —CH═CH— 293.411 305.422 294.42 306.18 301 302

CH₂ —CH═CH— 321.465 333.476 322.49 334.25 303 304

CH₂ —CH═CH— 309.366 321.377 310.38 322.17 306 306

CH₂ —CH═CH— 365.474 377.485 366.46 378.24 307 308

CH₂ —CH═CH— 339.439 351.45 340.43 352.2 309 310

CH₂ —CH═CH— 383.37 395.381 384.42 396.15 311 312

CH₂ —CH═CH— 335.354 347.365 336.37 348.11 313 314

CH₂ —CH═CH— 342.443 354.454 343.44 355.2 315

CH₂ 300.362 301.38 316 317

CH₂ —CH═CH— 357.498 369.509 358.46 370.27 318 319

CH₂ —CH═CH— 353.344 365.355 354.39 366.13 320 321

CH₂ —CH═CH— 319.427 331.438 320.37 332.15 322 323

CH₂ —CH═CH— 329.4 341.411 330.47 342.19 324 325

CH₂ —CH═CH— 335.354 347.365 336.46 348.17 326 327

CH₂ —CH═CH— 341.455 353.466 342.44 354.21 328 329

CH₂ —CH═CH— 305.4 317.411 306.34 318.14 330 331

CH₂ —CH═CH— 335.354 347.365 336.37 348.12 332 333

CH₂ —CH═CH— 335.354 347.365 336.43 348.16

TABLE 3

Example No. R X Mol Wt [M + H]+ 334 CH₃ CH₂CH₂ 249.314 250.24 335 CF₂271.267 271.41 336 337 338

CH₂ CH₂CH₂ CF₂ 297.358 311.385 333.338 298.37 312.25 334.4 339 340

CH₂CH₂ CF₂ 345.83 367.783 346.22 368.36 341 342 343

CH₂ CH₂CH₂ CF₂ 331.803 345.83 367.783 332.33 346.21 368.35 344 345 346

CH₂ CH₂CH₂ CF₂ 331.803 345.83 367.783 332.36 346.22 368.41 347 348

CH₂ CH₂CH₂ 366.248 380.275 366.3 380.2 349 350 351

CH₂ CH₂CH₂ CF₂ 366.248 380.275 402.228 366.31 380.17 402.42 35

CH₂ 366.248 366.29 353 354 355

CH₂ CH₂CH₂ CF₂ 315.348 329.375 351.328 316.36 330.21 352.39 356 357 358

CH₂ CH₂CH₂ CF₂ 315.348 329.375 351.328 316.39 330.25 352.34 359 360 361

CH₂ CH₂CH₂ CF₂ 327.384 341.411 363.364 328.39 342.23 364.39 362 363

CH₂CH₂ CF₂ 341.411 363.364 342.26 364.4 364 365 366

CH₂ CH₂CH₂ CF₂ 311.385 325.412 347.365 312.38 326.29 348.38 367 368 369

CH₂ CH₂CH₂ CF₂ 311.385 325.412 347.365 312.39 326.26 348.38 370 371 372

CH₂ CH₂CH₂ CF₂ 311.385 325.412 347.365 312.38 326.26 348.41 373 374

CH₂ CH₂CH₂ 365.355 379.382 366.38 380.27 375 376

CH₂ CH₂CH₂ 342.355 356.382 343.36 357.26 377 378

CH₂CF₂ 347.418 383.398 348.4 384.38 379 380 381

CH₂ CH₂CH₂ CF₂ 347.418 361.445 383.398 348.39 362.29 384.42 382 383 384

CH₂ CH₂CH₂ CF₂ 353.466 367.493 389.446 354.43 368.33 390.46 385 386 387

CH₂ CH₂CH₂ CF₂ 315.348 329.375 351.328 316.34 330.26 352.41 388 389 390

CH₂ CH₂CH₂ CF₂ 366.248 380.275 402.228 366.3 380.2 402.29 391 392 393

CH₂ CH₂CH₂ CF₂ 365.355 379.382 401.335 366.36 380.24 402.37 394 395 396

CH₂ CH₂CH₂ CF₂ 376.259 390.286 412.239 376.29 390.16 412.2 397 398

CH₂ CF₂ 327.384 363.364 328.38 364.41 399 400 401

CH₂ CH₂CH₂ CF₂ 369.465 383.492 405.445 370.44 384.32 406.44 402 403 404

CH₂ CH₂CH₂ CF₂ 371.437 385.464 407.417 372.41 387.32 408.41 405 406 407

CH₂ CH₂CH₂ CF₂ 381.52 395.547 417.5 382.5 396.34 418.45 408 409 410

CH₂ CH₂CH₂ CF₂ 311.385 325.412 347.365 312.4 326.27 348.42 411 412 413

CH₂ CH₂CH₂ CF₂ 325.412 339.439 361.392 326.41 340.28 362.4 414

CH₂ 353.444 354.38 45 416 417

CH₂ CH₂CH₂ CF₂ 303.384 317.411 339.364 304.34 318.19 340.36 418 419 420

CH₂ CH₂CH₂ CF₂ 287.319 301.346 323.299 288.38 302.2 324.34 421

CF₂ 368.771 369.35 422 423 424

CH₂ CH₂CH₂ CF₂ 341.411 355.438 377.391 342.41 356.29 378.41 425 426

CH₂ CF₂ 303.406 339.386 304.4 340.4 427 428 429

CH₂ CH₂CH₂ CF₂ 289.379 303.406 325.359 290.4 304.27 326.45 430 431 432

CH₂ CH₂CH₂ CF₂ 275.352 289.379 311.332 276.41 290.27 312.39 433 434 435

CH₂ CH₂CH₂ CF₂ 261.325 275.352 297.305 262.39 276.25 298.38 436 437 438

CH₂ CH₂CH₂ CF₂ 303.406 317.433 339.386 304.43 318.27 340.45 439 440 441

CH₂ CH₂CH₂ CF₂ 277.368 291.395 313.348 278.45 292.25 314.4 442 443

CH₂ CF₂ 291.395 327.375 292.43 328.42 444 445

CH₂ CF₂ 291.395 327.375 292.43 328.44 446 447

CH₂ CF₂ 319.449 355.429 320.47 356.47 448

CH₂ 307.35 308.35 449 450

CH₂ CF₂ 363.458 399.438 364.44 400.46 451 452 453

CH₂ CH₂CH₂ CF₂ 337.423 351.45 373.403 338.41 352.24 374.43 454 455 456

CH₂ CH₂CH₂ CF₂ 381.354 395.381 417.334 382.39 396.23 418.31 457 458 459

CH₂ CH₂CH₂ CF₂ 333.338 347.365 369.318 334.37 348.23 370.36 460 461

CH₂ CF₂ 340.427 376.407 341.43 376.43 462

CF₂ 334.326 335.38 463 464 465

CH₂ CH₂CH₂ CF₂ 355.482 369.509 391.462 356.44 370.34 392.49 466 467

CH₂ CH₂CH₂ 351.328 365.355 352.36 366.21 468 469 470

CH₂ CH₂CH₂ CF₂ 317.411 331.438 353.391 318.33 332.2 354.36 471 472 473

CH₂ CH₂CH₂ CF₂ 327.384 341.411 363.364 328.38 342.27 364.4 474 475

CH₂ CH₂CH₂ 333.338 347.365 334.39 348.24 476 477 478

CH₂ CH₂CH₂ CF₂ 339.439 353.466 375.419 340.42 354.31 376.45 479 480 481

CH₂ CH₂CH₂ CF₂ 303.384 317.411 339.364 304.33 318.2 340.35 482 483

CH₂ CH₂CH₂ 333.338 347.365 334.37 348.22 484

CF₂ 389.424 390.34 485

CH₂ 333.338 334.41

TABLE 4

Example No R X′ Mol Wt [M + H]+ 486 CH₃ CH₂ 221.26  222.2  487 —CH═CH—233.271 234.07 488 489

CH₂ —CH═CH— 283.331 295.342 284.04 296.11 490 491

CH₂ —CH═CH— 317.776 329.787 318.12 330.11 492 493

CH₂ —CH═CH— 317.776 329.787 318.07 330.11 494 495

CH₂ —CH═CH— 317.776 329.787 318.11 330.13 496 497

CH₂ —CH═CH— 352.221 364.232 352.04 364.08 498 499

CH₂ —CH═CH— 352.221 364.232 352.09 364.05 500 501

CH₂ —CH═CH— 352.221 364.232 352.07 364.07 502 503

CH₂ —CH═CH— 301.321 313.332 302.09 314.13 504 505

CH₂ —CH═CH— 301.321 313.332 302.09 314.12 506 507

CH₂ —CH═CH— 313.357 325.368 314.16 326.16 508 509

CH₂ —CH═CH— 313.357 325.368 314.12 326.15 510 511

CH₂ —CH═CH— 327.34  339.351 328.08 339.51 512

—CH═CH— 309.369 310.14 513 514

CH₂ —CH═CH— 297.358 309.369 298.12 310.13 515 516

CH₂ —CH═CH— 297.358 309.369 298.1  310.13 517

—CH═CH— 320.352 321.09 518 519

CH₂ —CH═CH— 351.328 363.339 352.1  364.12 520

CH₂ 328.328 329.09 521

CH₂ 308.341 309.17 522 523

CH₂ —CH═CH— 333.391 345.402 334.18 346.15 524 525

CH₂ —CH═CH— 333.391 345.402 334.13 346.14 526 527

CH₂ —CH═CH— 339.439 351.45  340.2  352.2  528

—CH═CH— 371.44  371.17 529 530

CH₂ —CH═CH— 301.321 313.332 302.13 314.13 531 532

CH₂ —CH═CH— 352.221 364.232 352.04 364.04 533 534

CH₂ —CH═CH— 351.328 363.339 352.11 364.15 535 536

CH₂ —CH═CH— 362.232 374.243 362.06 374.05 537 538

CH₂ —CH═CH— 313.357 325.368 314.15 326.15 539 540

CH₂ —CH═CH— 355.438 367.449 356.17 368.19 541

—CH═CH— 340.339 341.2  542 543

CH₂ —CH═CH— 357.41  369.421 358.18 370.19 544 545

CH₂ —CH═CH— 367.493 379.504 368.24 380.26 546 547

CH₂ —CH═CH— 297.358 309.369 298.13 310.16 548 549

CH₂ —CH═CH— 311.385 323.396 312.17 324.13 550 551

CH₂ —CH═CH— 339.417 351.428 340.01 351.98 552 553

CH₂ —CH═CH— 289.357 301.368 290.07 302.09 554 555

CH₂ —CH═CH— 273.292 285.303 274.13 286.1  556 557

CH₂ —CH═CH— 327.384 339.395 328.21 340.18 558 559

CH₂ —CH═CH— 289.379 301.39  290.14 302.16 560 561

CH₂ —CH═CH— 275.352 287.363 276.12 288.18 562 563

CH₂ —CH═CH— 261.325 273.336 262.19 274.09 564 565

CH₂ —CH═CH— 247.298 259.309 248.09 260.07 566 567

CH₂ —CH═CH— 289.379 301.39  290.16 302.13 568 569

CH₂ —CH═CH— 263.341 275.352 264.17 276.18 570 571

CH₂ —CH═CH— 277.368 289.379 278.12 290.13 572 573

CH₂ —CH═CH— 277.368 289.379 278.13 290.17 574

—CH═CH— 317.433 318.21 575 576

CH₂ —CH═CH— 293.323 305.334 294.06 306.12 577 578

CH₂ —CH═CH— 349.431 361.442 350.24 362.21 579 580

CH₂ —CH═CH— 323.396 335.407 324.17 336.18 581 582

CH₂ —CH═CH— 367.327 379.338 368.11 380.15 583 584

CH₂ —CH═CH— 319.311 331.322 320.1  332.13 585 586

CH₂ —CH═CH— 326.4  338.411 327.16 339.19 587 588

CH₂ —CH═CH— 341.455 353.466 342.21 354.22 589 590

CH₂ —CH═CH— 337.301 349.312 338.14 350.12 591 592

CH₂ —CH═CH— 303.384 315.395 304.04 316.1  593 594

CH₂ —CH═CH— 313.357 325.368 314.16 326.17 595

CH₂ 319.311 320.14 596 597

CH₂ —CH═CH— 325.412 337.423 326.19 338.2  598 599

CH₂ —CH═CH— 289.357 301.368 290.08 302.05 600

—CH═CH— 331.322 332.17 601 602

CH₂ —CH═CH— 319.311 331.322 320.12 332.17

TABLE 5

Example No R R1 Mol Wt {M + H}+ 603 CH₃ Me 209.249 209.16 604 tBu251.33  252.5  605 iBu 251.33  252.4  606 nBu 251.33  250.95 607 Ph271.32  271.43 608 Ch 277.368 278.4  609 610 611 612 613 614

Me tBu iBu nBu Ph Ch 271.32  313.401 313.401 313.401 333.391 339.439272.24 314.45 313.89 314.18 334.36 340.35 615 616 617 618 619 620

Me tBu iBu nBu Ph Ch 305.765 347.846 347.846 347.846 367.836 373.884306.12 348.41 348.16 348.15 368.38 374.34 621 622 623 624 625 626 627

Me iPr tBu iBu nBu Ph Ch 305.765 333.819 347.846 347.846 347.846 367.836373.884 306.1  334.06 348.4  348.15 348.15 368.35 374.34 628 629 630 631632 633 634

Me iPr tBu iBu nBu Ph Ch 305.765 333.819 347.846 347.846 347.846 367.836373.884 306.18 332.89 348.45 348.16 348.13 368.37 374.33 635 636 637 638639 640

Me tBu iBu nBu Ph Ch 340.21  382.291 382.291 382.291 402.281 408.329340.06 382.44 382.13 382.06 402.36 408.28 641 642 643 644 645 646

Me iPr tBu nBu Ph Ch 340.21  368.264 382.291 382.291 402.281 408.329340.09 369.12 382.43 382.1  402.34 408.33 647 648 649 650 651 652 653

Me iPr tBu iBu nBu Ph Ch 340.21  368.264 382.291 382.291 382.291 402.281408.329 340.1  367.92 382.44 382.13 382.13 402.3  408.3  654 655 656 657658 659

Me tBu iBu nBu Ph Ch 289.31  331.391 331.391 331.391 351.381 357.429290.07 332.45 332.21 332.19 352.38 358.33 660 661 662 663 664 665

Me tBu iBu nBu Ph Ch 289.31 331.391 331.391 331.391 351.381 357.429290.07 332.44 332.22 332.15 352.4  358.34 666 667 668 669 670

Me tBu iBu nBu Ph 301.346 343.427 343.427 343.427 363.417 302.14 344.5 344.21 344.23 365.44 671 672 673 674 675

Me tBu nBu Ph Ch 301.346 343.427 343.427 363.417 369.465 302.11 344.51344.19 364.4  370.4  676 677 678

Me nBu Ph 315.329 357.41 377.4  316   359.15 379.52 679 680 681 682 683684 685

Me iPr tBu iBu nBu Ph Ch 285.347 313.401 327.428 327.428 327.428 347.418353.466 286.14 314.2  328.51 328.22 328.2  348.43 354.37 686 687 688 689690 691 692

Me iPr tBu iBu nBu Ph Ch 285.347 313.401 327.428 327.428 327.428 347.418353.466 286.14 314.34 328.48 328.17 328.22 348.4  354.38 693 694 695 696697 698

Me tBu iBu nBu Ph Ch 285.347 327.428 327.428 327.428 347.418 353.466286.06 328.51 328.19 328.16 348.43 354.38 699 700 701 702 703

Me iBu nBu Ph Ch 296.33  338.411 338.411 358.401 364.449 297.08 339.18339.2  359.37 365.36 704 705 706 707 708 709

Me iPr tBu nBu Ph Ch 339.317 367.371 381.398 381.398 401.388 407.436340.13 368.01 382.48 382.18 402.39 408.31 710 711 712 713

tBu iBu Ph Ch 358.398 358.398 378.388 384.436 359.46 359.23 379.41385.38 714 715 716 717 718 719 720

Me iPr tBu iBu nBu Ph Ch 321.38  349.434 363.461 363.461 363.461 383.451389.499 322.21 350.39 364.48 364.22 364.17 384.44 390.43 721 722 723 724725 726

Me iPr tBu iBu nBu Ch 321.38  349.434 363.461 363.461 363.461 389.499322.14 350.1  364.49 364.22 364.21 390.41 727 728 729 730 731 732

Me iPr tBu nBu Ph Ch 327.428 355.482 369.509 369.509 389.499 395.547328.2  355.78 370.56 370.26 390.51 396.46 733 734 735

Me nBu Ph 347.418 389.499 409.489 349.52 391.27 411.29 736 737 738 739740 741

Me tBu iBu nBu Ph Ch 289.31  331.391 331.391 331.391 351.381 357.429290.12 332.49 332.24 332.18 352.39 358.32 742 743 744 745 746 747 748

Me iPr tBu iBu nBu Ph Ch 340.21  368.264 382.291 382.291 382.291 402.281408.329 340.05 368.24 382.45 382.13 382.12 402.34 408.28 749 750 751 752753

Me tBu Bu Ph Ch 339.317 381.398 381.398 401.388 407.436 340.13 382.51382.19 402.38 408.34 754 755 756 757 758 759

Me tBu iBu nBu Ph Ch 350.221 392.302 392.302 392.302 412.292 418.34 350   392.44 392.12 392.09 412.29 418.24 760 761 762 763 764

Me iBu nBu Ph Ch 301.346 343.427 343.427 363.417 369.465 302.12 344.22344.18 364.42 370.39 765 766 767 768 769 770

Me iPr tBu nBu Ph Ch 343.427 371.481 385.508 385.508 405.498 411.546344.19 372.1  386.57 386.25 406.48 412.43 771 772 773

Me iBu nBu 316.317 358.398 358.398 317.09 359.21 359.19 774 775 776 777778 779

Me tBu iBu nBu Ph Ch 345.399 387.48  387.48  387.48  407.47  413.518346.16 388.57 388.24 388.24 408.43 414.38 780 781 782 783 784 785

Me iPr tBu nBu Ph Ch 355.482 383.536 397.563 397.563 417.553 423.601356.22 383.17 398.55 398.27 418.45 424.43 786 787 788 789 790 791 792

Me iPr tBu iBu nBu Ph Ch 285.347 313.401 327.428 327.428 327.428 347.418353.466 286.14 314.06 328.48 328.25 328.15 348.43 354.37 793 794 795 796797 798

Me tBu iBu nBu Ph Ch 299.374 341.455 341.455 341.455 361.445 367.493300.24 342.51 342.25 342.2  362.44 368.43 799 800 801

Me iPr tBu 327.406 355.46  369.487 328.14 356.36 370.45 802 803 804 805806 807

Me tBu iBu nBu Ph Ch 277.346 319.427 319.427 319.427 339.417 345.465277.98 320.42 320.16 320.21 340.38 346.3  808 809 810 811 812 813

Me tBu iBu nBu Ph Ch 261.281 303.362 303.362 303.362 323.352 329.4 262.1  304.44 304.19 304.14 324.36 330.37 814 815 816 817 818 819

Me tBu iBu nBu Ph Ch 306.753 348.834 348.834 348.834 368.824 374.872307   349.45 349.17 349.13 369.37 375.33 820 821 822 823 824 825

Me tBu iBu nBu Ph Ch 315.373 357.454 357.454 357.454 377.444 383.492316.14 358.49 358.22 358.19 378.45 384.43 826 827 828 829 830 831

Me iPr tBu iBu nBu Ch 277.368 305.422 319.449 319.449 319.449 345.487278.23 306.29 320.53 320.27 320.24 346.43 832 833 834 835 836 837 838

Me iPr tBu iBu nBu Ph Ch 263.341 291.395 305.422 305.422 305.422 325.412331.46  264.07 292.47 306.5  306.2  306.17 326.44 332.41 839 840 841 842843 844 845

Me iPr tBu iBu nBu Ph Ch 249.314 277.368 291.395 291.395 291.395 311.385317.433 250.16 278.43 292.52 292.19 292.15 312.39 318.42 846 847 848 849850 851 852

Me iPr tBu iBu nBu Ph Ch 235.287 263.341 277.368 277.368 277.368 297.358303.406 235.95 264.19 278.48 278.29 278.17 298.39 304.36 853 854 855 856857 858 859

Me iPr tBu iBu nBu Ph Ch 277.368 305.422 319.449 319.449 319.449 339.439345.487 278.13 307.66 320.53 320.25 320.26 340.44 346.4  860 861 862 863864 865 866

Me iPr tBu iBu nBu Ph Ch 251.33  279.384 293.411 293.411 293.411 313.401319.449 251.82 280.53 294.61 294.04 294.21 314.39 320.39 867 868 869 870871 872 873

Me iPr tBu iBu nBu Ph Ch 265.357 293.411 307.438 307.438 307.438 327.428333.476 266.16 293.92 308.5  308.24 308.26 328.46 334.42 874 875 876 877878 879 880

Me iPr tBu iBu nBu Ph Ch 265.357 293.411 307.438 307.438 307.438 327.428333.476 266.13 293.68 308.51 308.25 308.21 328.47 334.41 881 882 883 884885 886 887

Me iPr tBu iBu nBu Ph Ch 293.411 321.465 335.492 335.492 335.492 355.482361.53  294.24 322.51 336.54 335.79 336.26 356.49 362.43 888 889 890 891892

Me tBu iBu nBu Ch 281.312 323.393 323.393 323.393 349.431 282.04 324.49324.21 324.23 350.4  893 894 895 896 897 898 899

Me iPr tBu iBu nBu Ph Ch 337.42  365.474 379.501 379.501 379.501 399.491405.539 338.17 366.21 380.62 380.26 380.27 400.49 406.43 900 901 902 903904 905 906

Me iPr tBu iBu nBu Ph Ch 311.385 339.439 353.466 353.466 353.466 373.456379.504 312.14 340.12 354.52 354.24 354.2  374.45 380.41 907 908 909 910911 912 913

Me iPr tBu iBu nBu Ph Ch 355.316 383.37 397.397 397.397 397.397 417.387423.435 356.09 384.24 398.49 398.2  398.19 418.36 424.32 914 915 916 917918 919 920

Me iPr tBu iBu nBu Ph Ch 307.3  335.354 349.381 349.381 349.381 369.371375.419 308.06 335.12 350.49 350.2  350.12 370.4  376.38 921 922 923 924925 926

Me iPr tBu iBu nBu Ch 314.389 342.443 356.47  356.47  356.47  382.508315.11 343.02 357.49 357.27 357.21 383.42 927 928 929 930 931 932 933

Me iPr tBu iBu nBu Ph Ch 272.308 300.362 314.389 314.389 314.389 334.379340.427 273.08 301.02 315.46 315.17 315.2  335.4  341.37 934 935 936

Me iBu Ch 272.308 314.389 340.427 273.07 315.18 341.36 937 938 939 940941

Me tBu nBu Ph Ch 329.444 371.525 371.525 391.515 397.563 330.22 372.57372.29 392.49 398.44 942 943 944 945 946 947 948

Me iPr tBu iBu nBu Ph Ch 325.29  353.344 367.371 367.371 367.371 387.361393.409 326.09 354.29 368.44 368.18 368.15 388.39 394.38 949 950 951 952953 954 955

Me iPr tBu iBu nBu Ph Ch 291.373 319.427 333.454 333.454 333.454 353.444359.492 292.13 320.15 334.45 334.2  334.21 354.34 360.35 956 957 958 959960 961 962

Me iPr tBu iBu nBu Ph Ch 301.346 329.4  343.427 343.427 343.427 363.417369.465 302.11 330.13 344.5  344.22 344.17 364.41 370.42 963 964 965 966

tBu iBu Ph Ch 349.381 349.381 369.371 375.419 350.39 350.12 370.41376.36 967 968 969 970 971 972

Me tBu iBu nBu Ph Ch 277.346 319.427 319.427 319.427 339.417 345.465278.08 320.35 320.18 320.21 340.34 346.31 973 974 975 976 977 978 979

Me iPr tBu iBu nBu Ph Ch 307.3  335.354 349.381 349.381 349.381 369.371375.419 308.05 336.21 350.46 350.2  350.16 370.37 376.37 980

iPr 355.46  355.93 981 982 983 984

tBu iBu Ph Ch 349.381 349.381 369.371 375.419 350.4  350.24 370.41376.43

TABLE 6

Example No R AA Mol Wt [M + H]+ 985 CH₃ Oic 289.379 289.39 986 987

Tic Oic 359.429 351.45  360.28 352.4  988 989 990

Tic Pic Oic 393.874 345.83  385.895 394.31 346.18 386.4  991 992

Tic Oic 393.874 385.895 394.29 386.39 993 994

Tic Oic 393.874 385.895 394.3  386.38 995 996

Tic Oic 428.319 420.34  428.19 420.32 997 998 999

Tic Pic Oic 428.319 380.275 420.34  428.2  380.22 420.31 1000 1001

Tic Oic 428.319 420.34  428.19 420.3  1002 1003

Pic Oic 329.375 369.44  330.33 370.4  1004 1005

Tic Oic 377.419 369.44  378.31 370.41 1006 1007 1008

Tic Pic Oic 389.455 341.411 381.476 390.32 342.27 382.43 1009 1010 1011

Tic Pic Oic 389.455 341.411 381.476 390.35 342.36 382.45 1012 1013 1014

Tic Pic Oic 373.456 325.412 365.477 374.34 326.38 366.41 1015 1016 1017

Tic Pic Oic 373.456 325.412 365.477 374.31 326.24 366.41 1018 1019

Tic Pic 373.456 325.412 374.34 326.31 1020 1021

Tic Oic 384.439 376.46  385.29 377.4  1022 1023

Tic Oic 427.426 419.447 428.27 420.38 1024 1025 1026

Tic Pic Oic 404.426 356.382 396.447 405.27 357.32 397.39 1027 1028 1029

Tic Pic Oic 409.489 361.445 401.51  410.32 362.36 402.44 1030 1031 1032

Tic Pic Oic 409.489 361.445 401.51  410.26 362.34 402.43 1033 1034 1035

Tic Pic Oic 415.537 367.493 407.558 416.35 368.34 408.47 1036

Tic 435.527 437.27 1037 1038 1039

Tic Pic Oic 377.419 329.375 369.44  378.34 330.3  370.4  1040 1041

Tic Oic 428.319 420.34  428.18 420.29 1042 1043

Tic Oic 427.426 419.447 428.27 420.38 1044 1045 1046

Tic Pic Oic 438.33  390.286 430.351 438.18 390.22 430.28 1047 1048 1049

Tic Pic Oic 389.455 341.411 381.476 390.34 342.37 382.43 1050 1051 1052

Tic Pic Oic 431.536 383.492 423.557 432.38 384.43 424.44 1053 1054 1055

Tic Pic Oic 433.508 385.464 425.529 434.31 386.34 426.4  1056 1057 1058

Tic Pic Oic 443.591 395.547 435.612 444.36 396.46 436.47 1059 1060 1061

Tic Pic Oic 373.456 325.412 365.477 374.36 326.36 366.43 1062 1063

Tic Oic 387.483 379.504 388.38 380.46 1064 1065

Tic Oic 365.455 357.476 366.27 358.36 1066 1067

Tic Oic 349.39  341.411 350.27 342.38 1068 1069 1070

Tic Pic Oic 394.862 346.818 386.883 395.29 347.24 387.39 1071 1072 1073

Tic Pic Oic 403.482 355.438 395.503 404.33 356.35 396.45 1074 1075 1076

Tic Pic Oic 365.477 317.433 357.498 366.4  318.24 358.46 1077 1078 1079

Tic Pic Oic 351.45  303.406 343.471 352.35 304.33 344.43 1080 1081 1082

Tic Pic Oic 337.423 289.379 329.444 338.32 290.29 330.41 1083 1084 1085

Tic Pic Oic 323.396 275.352 315.417 324.31 276.29 316.41 1086 1087

Tic Oic 365.477 357.498 366.38 358.46 1088

Oic 331.46  332.41 1089 1090 1091

Tic Pic Oic 353.466 305.422 345.487 354.34 306.41 346.45 1092 1093

Tic Oic 353.466 345.487 354.35 346.45 1094 1095 1096

Tic Pic Oic 381.52  333.476 373.541 382.4  334.45 374.49 1097 1098 1099

Tic Pic Oic 369.421 321.377 361.442 370.32 322.25 362.41 1100 1101 1102

Tic Pic Oic 425.529 377.485 417.55  426.33 378.37 418.45 1103 1104 1105

Tic Pic Oic 399.494 351.45  391.515 400.35 352.33 392.47 1106 1107 1108

Tic Pic Oic 443.425 395.381 435.446 444.28 396.35 436.37 1109 1110 1111

Tic Pic Oic 395.409 347.365 387.43  396.31 348.28 388.43 1112 1113

Pic Oic 354.454 394.519 354.35 395.47 1114 1115 1116

Tic Pic Oic 360.417 312.373 352.438 361.3  313.26 353.38 1117 1118

Tic Oic 360.417 352.438 361.29 353.41 1119 1120

Tic Oic 417.553 409.574 418.36 410.46 1121 1122

Tic Oic 413.399 405.42  414.2  406.37 1123 1124 1125

Tic Pic Oic 379.482 331.438 371.503 380.32 332.31 372.39 1126 1127 1128

Tic Pic Oic 389.455 341.411 381.476 390.34 342.36 382.45 1129 1130 1131

Tic Pic Oic 395.409 347.365 387.43  396.33 348.31 388.38 1132 1133 1134

Tic Pic Oic 401.51  353.466 393.531 402.38 354.33 394.47 1135 1136 1137

Tic Pic Oic 365.455 317.411 357.476 366.3  318.27 358.35 1138 1139 1140

Tic Pic Oic 395.409 347.365 387.43  396.28 348.27 388.41 1141 1142

Tic Oic 395.409 387.43  396.33 388.42

TABLE 7

Example No R R2 Mol Wt [M + H]+ 1143 CH₃ tBu 265.357 266.24 1144 Ph285.347 286.35 1145 Ch 291.395 292.36 1146 OCH₂Ph 315.373 315.47 1147CH₂CO₂CH₂Ph 357.41  357.46 1148 1149 1150 1151 1152 1153

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 327.428 347.418 353.466 377.444329.356 419.481 328.25 348.36 354.35 378.49 330.16 420.46 1154 1155 11561157 1158 1159

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 361.873 381.863 387.911 411.889363.801 453.926 362.2  382.34 388.33 412.4  364.11 454.44 1160 1161 11621163 1164 1165

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 361.873 381.863 387.911 411.889363.801 453.926 362.19 382.31 388.35 412.4  364.14 454.42 1166 1167 11681169 1170 1171

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 361.873 381.863 387.911 411.889363.801 453.926 362.23 382.36 388.34 412.4  364.14 454.43 1172 1173 11741175 1176 1177

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 396.318 416.308 422.356 446.334398.246 488.371 396.16 416.29 422.24 446.35 398.13 488.36 1178 1179 11801181 1182 1183

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 396.318 416.308 422.356 446.334398.246 488.371 396.15 416.24 422.25 446.36 398.07 488.32 1184 1185 11861187 1188 1189

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 396.318 416.308 422.356 446.334398.246 488.371 396.17 416.28 422.27 446.37 398.04 488.33 1190 1191 11921193 1194 1195

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 345.418 365.408 371.456 395.434347.346 437.471 346.24 366.34 372.34 396.47 348.2  438.44 1196 1197 11981199 1200 1201

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 345.418 365.408 371.456 395.434347.346 437.471 346.25 366.34 372.35 396.46 348.19 438.42 1202 1203 12041205 1206

tBu Ph Ch OCH₂Ph CH₂CO₂CH₂Ph 357.454 377.444 383.492 407.47  449.507358.25 378.4  384.39 408.49 450.49 1207 1208 1209 1210 1211 1212

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 357.454 377.444 383.492 407.47 359.382 449.507 358.24 378.38 384.39 408.46 360.16 450.48 1213 1214 12151216 1217 1218

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 341.455 361.445 367.493 391.471343.383 433.508 342.28 362.36 368.37 392.51 344.21 434.47 1219 1220 12211222 1223 1224

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 341.455 361.445 367.493 391.471343.383 433.508 342.26 362.36 368.35 392.52 344.16 434.43 1225 1226 12271228 1229 1230

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 341.455 361.445 367.493 391.471343.383 433.508 342.25 362.37 368.33 392.52 344.19 434.45 1231 1232 12331234 1235

Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 372.428 378.476 402.454 354.366 444.491373.38 379.35 403.46 355.15 445.48 1236 1237 1238 1239 1240 1241

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 395.425 415.415 421.463 445.441397.353 487.478 396.25 416.32 422.33 446.46 398.19 488.43 1242 1243 12441245 1246

Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 392.415 398.463 422.441 374.353 464.478393.36 399.34 423.42 375.19 465.47 1247 1248 1249 1250 1251 1252

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 377.488 397.478 403.526 427.504379.416 469.541 378.26 398.4  404.38 428.43 380.2  470.47 1253 1254 12551256 1257 1258

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 377.488 397.478 403.526 427.504379.416 469.541 378.26 398.39 404.37 428.45 380.25 470.49 1259 1260 12611262 1263 1264

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 383.536 403.526 409.574 433.552385.464 475.589 384.31 404.41 410.42 434.52 386.19 476.52 1265 1266 12671268 1269 1270

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 345.418 365.408 371.456 395.434347.346 437.471 346.24 366.34 372.35 396.48 348.17 438.44 1271 1272 12731274 1275 1276

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 396.318 416.308 422.356 446.334398.246 488.371 396.16 416.26 422.26 446.35 398.09 488.39 1277 1278 12791280 1281 1282

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 395.425 415.415 421.463 445.441397.353 487.478 396.22 416.33 422.32 446.44 398.18 488.44 1283 1284 12851286 1287

tBu Ph OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 406.329 426.319 456.345 408.257 498.382406.14 426.23 456.36 408.1  498.38 1288 1289 1290 1291 1292 1293

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 357.454 377.444 383.492 407.47 359.382 449.507 358.25 378.4  384.37 408.46 360.16 450.47 1294 1295 12961297 1298 1299

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 399.535 419.525 425.573 449.551401.463 491.588 400.3  420.41 426.4  450.52 402.28 492.51 1300 1301 1302

Ch OCH₂Ph CO₂CH₃ 398.463 422.441 374.353 399.32 423.46 375.21 1303 13041305 1306 1307 1308

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 401.507 421.497 427.545 451.523403.435 493.56  402.27 422.34 428.37 452.49 404.19 494.48 1309 1310 13111312 1313 1314

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 411.59  431.58  437.628 461.606413.518 503.643 412.33 432.42 438.44 462.55 414.25 504.56 1315 1316 13171318 1319 1320

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 341.455 361.445 367.493 391.471343.383 433.508 342.27 362.37 368.36 392.49 344.2  434.47 1321 1322 13231324 1325

tBu Ph OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 355.482 375.472 405.498 357.41  447.535356.27 376.42 406.46 358.21 448.47 1326 1327 1328 1329

tBu Ch CO₂CH₃ CH₂CO₂CH₂Ph 383.514 409.552 385.442 475.567 384.23 410.26386.17 476.46 1330 1331 1332 1333 1334 1335

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 333.454 353.444 359.492 383.47 335.382 425.507 334.22 354.29 360.31 384.46 336.12 426.37 1336 1337 13381339 1340 1341

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 317.389 337.379 343.427 367.405319.317 409.442 318.25 338.32 344.32 368.48 320.2  410.45 1342 1343 13441345 1346

Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 382.851 388.899 412.877 364.789 454.914383.32 389.33 413.38 365.13 455.43 1347 1348 1349 1350 1351

tBu Ph OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 371.481 391.471 421.497 373.409 463.534372.26 392.4  422.46 374.21 464.48 1352 1353 1354 1355 1356 1357

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 333.476 353.466 359.514 383.492335.404 425.529 334.31 354.42 360.39 384.53 336.28 426.48 1358 1359 13601361 1362 1363

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 319.449 339.439 345.487 369.465321.377 411.502 320.28 340.39 346.37 370.52 322.17 412.48 1364 1365 13661367 1368 1369

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 305.422 325.412 331.46  355.438307.35  397.475 306.25 326.36 332.36 356.49 308.22 398.49 1370 1371 13721373 1374 1375

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 291.395 311.385 317.433 341.411293.323 383.448 292.25 312.37 318.32 342.46 294.19 384.5  1376 1377 13781379 1380 1381

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 333.476 353.466 359.514 383.492335.404 425.529 334.3  354.38 360.4  384.56 336.22 426.48 1382 1383 13841385 1386 1387

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 307.438 371.428 333.476 357.454309.366 399.491 308.26 328.37 334.39 358.48 310.58 400.54 1388 1389 13901391 1392 1393

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 321.465 341.455 347.503 371.481323.393 413.518 322.29 342.42 348.39 372.52 324.24 414.51 1394 1395 13961397 1398

tBu Ph OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 321.465 341.455 371.481 323.393 413.518322.31 342.42 372.51 324.28 414.49 1399 1400 1401 1402 1403 1404

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 349.519 369.509 375.557 399.535351.447 441.572 350.33 370.44 376.43 400.55 352.3  442.55 1405 1406 14071408 1409

tBu Ph Ch OCH₂Ph CO₂CH₃ 337.42  357.41  363.458 387.436 339.348 338.26358.36 364.36 388.42 340.14 1410 1411 1412 1413 1414 1415

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 393.528 413.518 419.566 443.544395.456 485.581 394.32 414.4  420.4  444.5  396.25 486.52 1416

tBu 411.424 412.22 1417 Ph 431.414 432.29 1418 Ch 437.462 438.29 1419OCH₂Ph 461.44  462.46 1420 CO₂CH₃ 413.352 414.14 1421 CH₂CO₂CH₂Ph503.477 504.44 1422 1423 1424 1425 1426

tBu Ph Ch OCH₂Ph CH₂CO₂CH₂Ph 370.497 390.487 396.535 420.513 462.55 371.28 391.42 397.39 421.44 463.51 1427 1428 1429 1430 1431 1432

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 328.416 348:406 354.454 378.432330.344 420.469 329.27 349.37 355.32 379.47 331.13 421.43 1433 1434 14351436

Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 354.454 378.432 330.344 420.469 355.35379.53 331.14 421.46 1437 1438 1439 1440 1441 1442

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 385.552 405.542 411.59  435.568387.48  477.605 386.32 406.45 412.42 436.51 388.29 478.53 1443 1444 14451446 1447 1448

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 381.398 401.388 407.436 431.414383.326 473.451 382.21 402.35 408.3  432.37 384.16 474.46 1449 1450 14511452 1453

Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 367.471 373.519 397.497 349.409 439.534368.34 374.35 398.43 350.17 440.45 1454 1455 1456 1457 1458

tBu Ph OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 357.454 377.444 407.47  359.382 449.507358.26 378.39 408.48 360.21 450.49 1459 1460 1461 1462 1463 1464

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 363.408 383.398 389.446 413.424365.336 455.461 364.22 384.34 390.34 414.46 366.13 456.44 1465 1466 14671468 1469 1470

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 369.509 389.499 395.547 419.525371.437 461.562 370.3  390.43 396.41 420.48 372.23 462.52 1471 1472 14731474 1475 1476

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 333.454 353.444 359.492 383.47 335.382 425.507 334.22 354.3  360.32 384.46 336.09 426.4  1477 1478 14791480 1481 1482

tBu Ph Ch OCH₂Ph CO₂CH₃ CH₂CO₂CH₂Ph 363.408 383.398 389.446 413.424365.336 455.461 364.23 384.35 390.37 414.44 366.09 456.46 1483 1484

tBu CH₂CO₂CH₂Ph 383.514 475.567 384.22 476.43 1485 1486 1487 1488

tBu Ph OCH₂Ph CH₂CO₂CH₂Ph 363.408 383.398 413.424 455.461 364.22 384.3 414.42 456.43

TABLE 8

Example No R n Mol Wt [M + H]+ 1489 CH₃ 2 372.425 373.3  1490 1 358.398359.2  1491 1492 1493 1494

2 1 3 4 434.496 420.469 448.523 462.55  435.27 421.2  449.45 463.42 14951496 1497 1498

2 1 3 4 468.941 454.914 482.968 496.995 469.22 455.16 483.3  497.37 14991500 1501 1502

2 1 3 4 468.941 454.914 482.968 496.995 469.3  455.17 483.32 497.36 15031504 1505 1506

2 1 3 4 468.941 454.914 482.968 496.995 469.24 455.16 483.34 497.4  15071508 1509 1510

2 1 3 4 503.386 489.359 517.413 531.44  503.24 489.1  517.32 531.36 15111512 1513

2 1 4 503.386 489.359 531.44  503.21 489.1  531.34 1514 1515

3 4 517.413 531.44  517.33 531.33 1516 1517 1518 1519

2 1 3 4 452.486 438.459 466.513 480.54  453.33 439.18 467.39 481.41 15201521 1522 1523

2 1 3 4 452.486 438.459 466.513 480.54  453.33 439.2  467.35 481.38 15241525 1526

2 1 4 464.522 450.495 492.576 465.34 451.21 493.43 1527 1528 1529

2 1 3 464.522 450.495 478.549 465.35 451.21 479.37 1530 1531 1532 1533

2 1 3 4 448.523 434.496 462.55  476.577 449.28 435.2  463.44 477.43 15341535 1536 1537

2 1 3 4 448.523 434.496 462.55  476.577 449.29 435.21 463.41 477.41 15381539 1540 1541

2 1 3 4 448.523 434.496 462.55  476.577 449.27 435.22 463.38 477.43 15421543

3 4 473.533 487.56  474.39 488.41 1544 1545 1546 1547

2 1 3 4 502.493 488.466 516.52  530.547 503.33 489.16 517.35 531.41 15481549 1550 1551

2 1 3 4 479.493 465.466 493.52  507.547 480.31 466.19 494.35 508.4  15521553 1554 1555

2 1 3 4 484.556 470.529 498.583 512.61  485.34 471.2  499.41 513.43 15561557 1558 1559

2 1 3 4 484.556 470.529 498.583 512.61  485.35 471.2  499.41 513.45 15601561 1562 1563

2 1 3 4 490.604 476.577 504.631 518.658 491.39 477.25 505.44 519.5  15641565 1566 1567

2 1 3 4 452.486 438.459 466.513 480.54  453.33 439.18 467.33 481.4  15681569 1570 1571

2 1 3 4 503.386 489.359 517.413 531.44  503.23 489.09 517.28 531.35 15721573 1574 1575

2 1 3 4 502.493 488.466 516.52  530.547 503.35 489.16 517.4  531.4  15761577 1578 1579

2 1 3 4 513.397 499.37  527.424 541.451 513.22 499.1  527.27 541.32 15801581

3 4 478.549 492.576 479.4  493.4  1582 1583 1584 1585

2 1 3 4 506.603 492.576 520.63  534.657 507.34 493.25 521.46 535.49 15861587 1588 1589

2 1 3 4 508.575 494.548 522.602 536.629 509.36 495.23 523.44 537.44 15901591 1592 1593

2 1 3 4 518.658 504.631 532.685 546.712 519.42 505.31 533.43 547.49 15941595 1596 1597

2 1 3 4 448.523 434.496 462.55  476.577 449.29 435.21 463.4  477.43 15981599 1600 1601

2 1 3 4 462.55  448.523 476.577 490.604 463.36 449.24 477.4  491.45 16021603 1604 1605

2 1 3 4 440.522 426.495 454.549 468.576 441.28 427.16 455.33 469.39 16061607 1608 1609

2 1 3 4 424.457 410.43  438.484 452.511 425.24 411.19 439.32 453.41 16101611

3 4 483.956 497.983 484.34 498.4  1612 1613 1614 1615

2 1 3 4 478.549 464.522 492.576 506.603 479.35 465.2  493.41 507.45 16161617 1618 1619

2 1 3 4 440.544 426.517 454.571 468.598 441.31 427.24 455.44 469.45 16201621 1622 1623

2 1 3 4 426.517 412.49  440.544 454.571 427.29 413.24 441.43 455.45 16241625 1626 1627

2 1 3 4 412.49  398.463 426.517 440.544 413.3  399.23 427.4  441.44 16281629 1630 1631

2 1 3 4 398.463 384.436 412.49  426.517 399.29 385.23 413.34 427.39 16321633 1634 1635

2 1 3 4 440.544 426.517 454.571 468.598 441.3  427.24 455.39 469.42 16361637 1638 1639

2 1 3 4 414.506 400.479 428.533 442.56  415.29 401.25 429.39 443.46 16401641

3 4 442.56  456.587 443.44 457.47 1642 1643 1644

1 3 4 414.506 442.56  456.587 415.24 443.42 457.48 1645 1646 1647 1648

2 1 3 4 456.587 442.56  470.614 484.641 457.41 443.28 471.46 485.48 16491650

3 4 458.515 472.542 459.41 473.43 1651 1652 1653

1 3 4 486.569 514.623 528.65  487.24 515.41 529.5  1654 1655 1656 1657

2 1 3 4 474.561 460.534 488.588 502.615 475.38 461.24 489.4  503.45 16581659 1660 1661

2 1 3 4 518.492 504.465 532.519 546.546 519.3  505.19 533.37 547.39 16621663 1664 1665

2 1 3 4 470.476 456.449 484.503 498.53  471.31 457.18 485.35 499.42 16661667 1668 1669

2 1 3 4 477.565 463.538 491.592 505.619 478.36 464.23 492.45 506.42 16701671

3 4 449.511 463.538 450.4  464.42 1672 1673

3 4 449.511 463.538 450.39 464.38 1674 1675 1676

2 1 4 492.62  478.593 520.674 493.41 479.27 521.51 1677 1678 1679 1680

2 1 3 4 488.466 474.439 502.493 516.52  489.29 475.16 503.35 517.42 16811682 1683 1684

2 1 3 4 454.549 440.522 468.576 482.603 455.3  441.14 469.37 483.37 16851686 1687 1688

2 1 3 4 464.522 450.495 478.549 492.576 465.3  451.2  479.39 493.42 16891690 1691 1692

2 1 3 4 470.476 456.449 484.503 498.53  471.32 457.19 485.34 499.39 16931694 1695 1696

2 1 3 4 476.577 462.55  490.604 504.631 477.38 463.23 491.41 505.46 16971698 1699 1700

2 1 3 4 440.522 426.495 454.549 468.576 441.27 427.15 455.32 469.36 17011702 1703 1704

2 1 3 4 470.476 456.449 484.503 498.53  471.25 457.18 485.37 499.39 1705

3 504.609 505.37 1706 1707 1708 1709

2 1 3 4 470.476 456.449 484.503 498.53  471.3  457.18 485.38 499.39

TABLE 9

Example No R R3 Mol Wt [M + H]+ 1710 CH₃ H 209.249 209.36 1711 Me223.276 223.34 1712

H 271.32  272.36 1713 1714

H CH₂Ph 305.765 395.89  306.25 396.33 1715 1716

H CH₂Ph 305.765 395.89  306.27 396.31 1717 1718

H CH₂Ph 305.765 395.89  306.29 396.28 1719 1720

H CH₂Ph 340.21  430.335 340.23 430.21 1721 1722 1723 1724

H Me secBu CH₂Ph 340.21  354.237 396.318 430.335 340.23 354.25 396.15430.2  1725 1726 1727

H Me CH₂Ph 340.21  354.237 430.335 340.24 354.24 430.28 1728 1729

H CH₂Ph 289.31  379.435 290.32 380.32 1730 1731

H CH₂Ph 289.31  379.435 290.28 380.32 1732 1733 1734 1735

H Me secBu CH₂Ph 301.346 315.373 357.454 391.471 302.37 316.34 358.27392.36 1736 1737 1738 1739

H Me secBu CH₂Ph 301.346 315.373 357.454 391.471 302.31 316.33 358.25392.37 1740 1741

H CH₂Ph 285.347 375.472 286.33 376.34 1742 1743 1744 1745

H Me secBu CH₂Ph 285.347 299.374 341.455 375.472 286.35 300.33 342.24376.36 1746 1747 1748

H Me CH₂Ph 285.347 299.374 375.472 286.33 300.32 376.36 1749 1750

H CH₂Ph 296.33  386.455 297.29 387.27 1751 1752

H CH₂Ph 339.317 429.442 340.32 430.29 1753 1754 1755

H Me CH₂Ph 316.317 330.344 406.442 317.31 331.35 407.31 1756 1757 1758

H Me CH₂Ph 321.38  335.407 411.505 322.33 336.35 412.32 1759 1760 17611762

H Me secBu CH₂Ph 321.38  335.407 377.488 411.505 322.33 336.37 378.31412.31 1763 1764 1765 1766

H Me secBu CH₂Ph 327.428 341.455 383.536 417.553 328.38 342.37 384.31418.4  1767 1768

H CH₂Ph 289.31  379.435 290.32 380.32 1769 1770

H CH₂Ph 340.21  430.335 340.24 430.25 1771 1772 1773

H secBu CH₂Ph 339.317 395.425 429.442 340.29 396.3  430.31 1774 17751776 1777

H Me secBu CH₂Ph 350.221 364.248 406.329 440.346 350.27 364.22 406.2 440.17 1778 1779 1780

H Me CH₂Ph 301.346 315.373 391.471 302.3  316.4  392.35 1781 1782 17831784

H Me secBu CH₂Ph 343.427 357.454 399.535 433.552 344.39 358.38 400.32434.36 1785 1786 1787

H Me CH₂Ph 345.399 359.426 435.524 346.36 360.33 436.37 1788 1789 17901791

H Me secBu CH₂Ph 355.482 369.509 411.59  445.607 356.42 370.4  412.34446.42 1792 1793

H CH₂Ph 285.347 375.472 286.32 376.34 1794 1795

H CH₂Ph 299.374 389.499 300.34 390.36 1796 1797 1798

H Me CH₂Ph 277.346 291.373 367.471 278.28 292.25 368.3  1799 1800

H CH₂Ph 261.281 351.406 262.34 352.32 1801 1802 1803 1804

H Me secBu CH₂Ph 315.373 329.4  371.481 405.498 316.34 330.38 372.3 406.31 1805

H 277.368 278.38 1806 1807

H CH₂Ph 263.341 353.466 264.38 354.34 1808 1809

H CH₂Ph 249.314 339.439 250.38 340.32 1810 1811

H CH₂Ph 235.287 325.412 236.33 326.34 1812 1813

H CH₂Ph 277.368 367.493 278.38 368.34 1814 1815

H CH₂Ph 251.33  341.455 252.36 342.31 1816 1817

H CH₂Ph 265.357 355.482 266.42 356.3  1818 1819

H CH₂Ph 265.357 355.482 266.38 356.34 1820 1821

H CH₂Ph 293.411 383.536 294.42 384.42 1822 1823 1824

H Me CH₂Ph 281.312 295.339 371.437 282.37 296.37 372.34 1825 1826

H CH₂Ph 337.42  427.545 338.37 428.39 1827 1828 1829 1830

H Me secBu CH₂Ph 311.385 325.412 367.493 401.51  312.34 326.29 368.26402.37 1831 1832 1833

H secBu CH₂Ph 355.316 411.424 445.441 356.3  412.22 446.3  1834 1835

H CH₂Ph 307.3  397.425 308.3  398.3  1836 1837

Me CH₂Ph 286.335 362.433 287.32 363.33 1838 1839 1840

H Me CH₂Ph 329.444 343.471 419.569 330.43 344.37 420.41 1841 1842

H CH₂Ph 325.29  415.415 326.26 416.26 1843 1844

H CH₂Ph 291.373 381.498 292.28 382.27 1845 1846

H CH₂Ph 301.346 391.471 302.32 392.34 1847 1848

H CH₂Ph 307.3  397.425 308.31 398.29 1849 1850

H CH₂Ph 313.401 403.526 314.37 404.42 1851 1852 1853

H Me CH₂Ph 277.346 291.373 367.471 278.29 292.29 368.26 1854 1855

H CH₂Ph 307.3  397.425 308.3  398.32

TABLE 10

Example No R′ Z X Mol Wt [M + H]+ 1855 Et O CH₂CH₂ 294.399 295.14 1856 OS 298.409 299.16 1857 iPr O CH₂ 294.399 295.51 1858 O CH₂CH₂ 308.426309.21 1859 O CF₂ 330.379 331.49 1860 nHex O CH₂ 336.48  337.56 1861 OCH₂CH₂ 350.507 351.29 1862 O S 354.517 355.2  1863 O CF₂ 372.46  373.531864 1865 1866 1867

O O O O CH₂ CH₂CH₂ S CF₂ 334.464 348.491 352.501 370.444 335.55 349.27353.2  371.54 1868 1869 1870 1871

O O O O CH₂ CH₂CH₂ S CF₂ 342.443 356.47  360.48  378.423 343.52 357.22361.16 379.5  1872 1873 1874 1875

O O O O CH₂ CH₂CH₂ S CF₂ 352.435 366.462 370.472 388.415 353.5  367.26371.16 389.49 1876 1877

O O CH₂CH₂ S 370.453 374.463 371.21 375.14 1878 1879 1880 1881

O O O O CH₂ CH₂CH₂ S CF₂ 328.416 342.443 346.453 364.396 329.5  343.24347.15 365.46 1882 1883 1884 1885

O O O O CH₂ CH₂CH₂ S CF₂ 358.442 372.469 376.479 394.422 359.5  373.21377.22 395.48 1886 1887 1888 1889

O O O O CH₂ CH₂CH₂ S CF₂ 342.443 356.47  360.48  378.423 343.51 357.23361.17 379.52 1890 1891 1892 1893

O O O O CH₂ CH₂CH₂ S CF₂ 397.306 411.333 415.343 433.286 397.47 411.15415.06 433.34 1894 1895 1896 1897

O O O O CH₂ CH₂CH₂ S CF₂ 346.406 360.433 364.443 382.386 347.5  361.18365.12 383.46 1898

O CH₂CH₂ 360.433 361.18 1899 1900 1901 1902

O O O O CH₂ CH₂CH₂ S CF₂ 346.406 360.433 364.443 382.386 347.43 361.22365.15 383.5  1903 1904 1905 1906

O O O O CH₂ CH₂CH₂ S CF₂ 378.476 392.503 396.513 414.456 379.5  393.23397.2  415.47 1907 1908 1909 1910

O O O O CH₂ CH₂CH₂ S CF₂ 396.413 410.44  414.45  432.393 397.49 411.21415.15 433.43 1911 1912 1913 1914

O O O O CH₂ CH₂CH₂ S CF₂ 362.861 376.888 380.898 398.841 363.45 377.18381.12 399.43 1915 1916 1917 1918

O O O O CH₂ CH₂CH₂ S CF₂ 362.861 376.888 380.898 398.841 363.47 377.2 381.12 399.45 1919 1920 1921 1922

O O O O CH₂ CH₂CH₂ S CF₂ 362.861 376.888 380.898 398.841 363.46 377.19381.11 399.45 1923 1924 1925 1926

O O O O CH₂ CH₂CH₂ S CF₂ 358.442 372.469 376.479 394.422 359.51 373.22377.17 395.54 1927 1928 1929 1930

O O O O CH₂ CH₂CH₂ S CF₂ 358.442 372.469 376.479 394.422 359.54 373.25377.18 395.51 1931 1932 1933 1934

O O O O CH₂ CH₂CH₂ S CF₂ 373.413 387.44  391.45  409.393 374.44 388.23392.15 410.45 1935 1936 1937 1938

O O O O CH₂ CH₂CH₂ S CF₂ 397.306 411.333 415.343 433.286 397.41 411.17415.09 433.34 1939 1940 1941 1942

O O O O CH₂ CH₂CH₂ S CF₂ 356.47  370.497 374.507 392.45  357.54 371.25375.19 393.52 1943 1944 1945 1946

O O O O CH₂ CH₂CH₂ S CF₂ 397.306 411.333 415.343 433.286 397.42 411.15415.05 433.38 1947 1948 1949 1950

O O O O CH₂ CH₂CH₂ S CF₂ 388.468 402.495 406.505 424.448 389.53 403.25407.15 425.48 1951 1952 1953 1954

O O O O CH₂ CH₂CH₂ S CF₂ 364.396 378.423 382.433 400.376 365.49 379.2 383.14 401.46 1955 1956 1957 1958

O O O O CH₂ CH₂CH₂ S CF₂ 404.514 418.541 422.551 440.494 405.51 419.23423.19 441.49 1959 nPr S CH₂ 310.464 311.48 1960 S CH₂ 324.491 325.221961 S S 328.501 329.11 1962 S CF₂ 346.444 347.49 1963 1964 1965 1966

S S S S CH₂ CH₂CH₂ S CF₂ 358.508 372.535 376.545 394.488 359.5  373.19377.16 395.46 1967 1968 1969

S S S CH₂CH₂ S CF₂ 386.562 390.572 408.515 387.22 391.17 409.45 19701971 1972 1973

S S S S CH₂ CH₂CH₂ S CF₂ 374.507 388.534 392.544 410.487 375.49 389.25393.15 411.43 1974 1975 1976 1977

O S S S CH₂ CH₂CH₂ S CF₂ 372.491 386.518 390.528 408.471 373.47 387.2 391.1  409.42 1978 1979 1980 1981

S S S S CH₂ CH₂CH₂ S CF₂ 336.502 350.529 354.539 372.482 337.52 351.19355.16 373.48 1982 1983 1984 1985

S S S S CH₂ CH₂CH₂ S CF₂ 364.556 378.583 382.593 400.536 365.59 379.24383.19 401.52

TABLE 11

Example No R′ Z X′ Mol Wt [M + H]+ 1986 Et O CH₂ 266.345 267.53 1987 O—CH═CH— 278.356 279.46 1988 iPr O CH₂ 280.372 281.53 1989 O —CH═CH—292.383 293.49 1990 nHex O CH₂ 322.453 323.53 1991 O —CH═CH— 334.464335.52 1992 1993

O O CH₂ —CH═CH— 320.437 332.448 321.53 333.49 1994 1995

O O CH₂ —CH═CH— 328.416 340.427 329.48 341.51 1996 1997

O O CH₂ —CH═CH— 338.408 350.419 339.57 351.5  1998

O CH₂ 342.399 343.59 1999 2000

O O CH₂ —CH═CH— 314.389 326.4  315.48 327.49 2001 2002

O O CH₂ —CH═CH— 344.415 356.426 345.49 357.49 2003 2004

O O CH₂ —CH═CH— 328.416 340.427 329.49 341.5  2005 2006

O O CH₂ —CH═CH— 383.279 395.29  383.45 395.4  2007 2008

O O CH₂ —CH═CH— 332.379 344.39  333.48 345.48 2009 2010

O O CH₂ —CH═CH— 332.379 344.39  333.48 345.47 2011 2012

O O CH₂ —CH═CH— 364.449 376.46  365.51 377.52 2013 2014

O O CH₂ —CH═CH— 382.386 394.397 383.46 395.48 2015 2016

O O CH₂ —CH═CH— 348.834 360.845 349.45 361.43 2017 2018

O O CH₂ —CH═CH— 348.834 360.845 349.47 361.43 2019 2020

O O CH₂ —CH═CH— 348.834 360.845 349.46 361.45 2021 2022

O O CH₂ —CH═CH— 344.415 356.426 345.51 357.5  2023 2024

O O CH₂ —CH═CH— 344.415 356.426 345.51 357.49 2025 2026

O O CH₂ —CH═CH— 359.386 371.397 360.47 372.47 2027 2028

O O CH₂ —CH═CH— 383.279 395.29  383.42 395.41 2029 2030

O O CH₂ —CH═CH— 342.443 354.454 343.47 355.49 2031 2032

O O CH₂ —CH═CH— 383.279 395.29  383.43 395.42 2033 2034

O O CH₂ —CH═CH— 374.441 386.452 375.54 387.54 2035 2036

O O CH₂ —CH═CH— 350.369 362.38  351.46 363.44 2037 2038

O O CH₂ —CH═CH— 390.487 402.498 391.56 403.51 2039 nPr S CH₂ 296.437297.49 2040 S —CH═CH— 308.448 309.44 2041 2042

S S CH₂ —CH═CH— 344.481 356.492 345.47 357.47 2043 2044

S S CH₂ —CH═CH— 358.508 370.519 359.49 371.52 2045 2046

S S CH₂ —CH═CH— 360.48  372.491 361.45 373.47 2047 2048

S S CH₂ —CH═CH— 358.464 370.475 359.49 371.43 2049 2050

S S CH₂ —CH═CH— 322.475 334.486 323.45 335.46 2051 2052

S S CH₂ —CH═CH— 350.529 362.54  351.57 363.53

TABLE 12

Example No R′ Z X Mol Wt [M + H]+ 2053 Et O CH₂ 264.329 265.11 2054 OCF₂ 300.309 301.42 2055 O CH₂CH₂ 278.356 279.25 2056 O CF₂ 314.336315.44 2057 O CH₂CH₂ 292.383 293.26 2058 nHex O CH₂ 320.437 321.19 2059O CF₂ 356.417 357.5  2060 O CH₂CH₂ 334.464 335.32 2061 2062 2063

O O O CH₂ CF₂ CH₂CH₂ 318.421 354.401 332.448 319.16 355.49 333.31 20642065 2066

O O O CH₂ CF₂ CH₂CH₂ 326.4  362.38  340.427 327.14 363.47 341.26 20672068 2069

O O O CH₂ CF₂ CH₂CH₂ 336.392 372.372 350.419 337.16 373.48 351.25 2070

O CH₂ 276.34  331.41 2071 2072

O O CH₂ CH₂CH₂ 340.383 354.41  341.1  355.26 2073 2074 2075

O O O CH₂ CF₂ CH₂CH₂ 312.373 348.353 326.4  313.09 349.44 327.28 20762077 2078

O O O CH₂ CF₂ CH₂CH₂ 342.399 378.379 356.426 343.24 379.48 357.27 20792080 2081

O O O CH₂ CF₂ CH₂CH₂ 326.4  362.38  340.427 327.14 363.49 341.29 20822083 2084

O O O CH₂ CF₂ CH₂CH₂ 381.263 417.243 395.29  381.09 417.24 395.17 20852086 2087

O O O CH₂ CF₂ CH₂CH₂ 330.363 366.343 344.39  331.14 367.43 345.27 20882089

O O CH₂ CH₂CH₂ 330.363 344.39  330.98 345.25 2090 2091 2092

O O O CH₂ CF₂ CH₂CH₂ 330.363 366.343 344.39  331.11 367.43 345.29 20932094 2095

O O O CH₂ CF₂ CH₂CH₂ 362.433 398.413 376.46  363.26 399.46 377.28 20962097 2098

O O O CH₂ CF₂ CH₂CH₂ 380.37  416.35  394.397 381.04 417.43 396.28 20992100 2101

O O O CH₂ CF₂ CH₂CH₂ 346.818 382.798 360.845 347.04 383.44 361.25 21022103 2104

O O O CH₂ CF₂ CH₂CH₂ 346.818 382.798 360.845 347.1  383.42 361.23 21052106 2107

O O O CH₂ CF₂ CH₂CH₂ 346.818 382.798 360.845 347.1  383.46 361.24 21082109 2110

O O O CH₂ CF₂ CH₂CH₂ 342.399 378.379 356.426 343.18 419.17 357.28 21112112 2113

O O O CH₂ CF₂ CH₂CH₂ 342.399 378.379 356.426 343.24 379.46 357.28 21142115 2116

O O O CH₂ CF₂ CH₂CH₂ 357.37  393.35  371.397 358.22 394.43 372.27 21172118 2119

O O O CH₂ CF₂ CH₂CH₂ 381.263 417.243 395.29  381.1  417.32 395.88 21202121 2122

O O O CH₂ CF₂ CH₂CH₂ 340.427 376.407 354.454 341.16 377.49 355.3  21232124 2125

O O O CH₂ CF₂ CH₂CH₂ 381.263 417.243 395.29  381.08 417.33 395.22 21262127 2128

O O O CH₂ CF₂ CH₂CH₂ 372.425 408.405 386.452 373.19 409.48 387.33 21292130 2131

O O O CH₂ CF₂ CH₂CH₂ 348.353 384.333 362.38  349.1  385.43 363.25 21322133 2134

O O O CH₂ CF₂ CH₂CH₂ 388.471 424.451 402.498 389.18 425.44 403.28 2135nPr S CH₂ 294.421 295.17 2136 S CF₂ 330.401 331.42 2137 2138 2139

S S S CH₂ CF₂ CH₂CH₂ 342.465 378.445 356.492 343.14 379.49 357.24 2140

S CH₂ 348.513 349.25

TABLE 13

Example No R′ Z X Mol Wt [M + H]+ 2141 Et O —CH═CH— 262.313 263.49 2142iPr O CH₂ 264.329 265.53 2143 O —CH═CH— 276.34  277.49 2144 nHex O CH₂306.41  307.52 2145 O —CH═CH— 318.421 319.49 2146 2147

O O CH₂ —CH═CH— 304.394 316.405 305.48 317.48 2148 2149

O O CH₂ —CH═CH— 312.373 324.384 313.48 325.46 2150 2151

O O CH₂ —CH═CH— 322.365 334.376 323.49 335.47 2152 2153

O O CH₂ —CH═CH— 298.346 310.357 299.45 311.44 2154 2155

O O CH₂ —CH═CH— 328.372 340.383 329.46 341.45 2156 2157

O O CH₂ —CH═CH— 312.373 324.384 313.45 325.45 2158 2159

O O CH₂ —CH═CH— 367.236 379.247 367.43 379.39 2160 2161

O O CH₂ —CH═CH— 316.336 328.347 317.45 329.44 2162

O —CH═CH— 328.347 329.33 2163 2164

O O CH₂ —CH═CH— 316.336 328.347 317.44 329.45 2165 2166

O O CH₂ —CH═CH— 348.406 360.417 349.46 361.45 2167 2168

O O CH₂ —CH═CH— 366.343 378.354 367.46 379.45 2169 2170

O O CH₂ —CH═CH— 332.791 344.802 333.42 345.41 2171 2172

O O CH₂ —CH═CH— 332.791 344.802 333.42 345.39 2173 2174

O O CH₂ —CH═CH— 332.791 344.802 333.42 345.42 2175 2176

O O CH₂ —CH═CH— 328.372 340.383 329.48 341.46 2177 2178

O O CH₂ —CH═CH— 328.372 340.383 329.46 341.46 2179 2180

O O CH₂ —CH═CH— 343.343 355.354 344.46 356.44 2181 2182

O O CH₂ —CH═CH— 367.236 379.247 367.36 379.37 2183 2184

O O CH₂ —CH═CH— 326.4  338.411 327.52 339.5  2185 2186

O O CH₂ —CH═CH— 367.236 379.247 367.41 379.39 2187 2188

O O CH₂ —CH═CH— 358.398 370.409 359.47 371.5  2189 2190

O O CH₂ —CH═CH— 334.326 346.337 335.42 347.44 2191 2192

O O CH₂ —CH═CH— 374.444 386.455 375.49 387.51 2193 nPr S CH₂ 280.394281.47 2194 S —CH═CH— 292.405 293.46 2195 2196

S S CH₂ —CH═CH— 328.438 340.449 329.49 341.45 2197 2198

S S CH₂ —CH═CH— 342.465 354.476 343.47 355.46 2199 2200

S S CH₂ —CH═CH— 344.437 356.448 344.45 357.48 2201 2202

S S CH₂ —CH═CH— 342.421 354.432 343.45 355.44 2203 2204

S S CH₂ —CH═CH— 306.432 318.443 307.38 319.47 2205 2206

S S CH₂ —CH═CH— 334.486 346.497 335.52 347.49

TABLE 14

Example No R′ Z R4 Mol Wt [M + H]+ 2207 Et O iBu 280.372 281.62 2208 OiPr 266.32  267.53 2209 O Ph 300.362 301.07 2210 O Me 238.291 239.542211 O tBu 280.372 267.53 2212 iPr O iBu 294.399 295.55 2213 O iPr280.372 281.45 2214 O Ph 314.389 315.03 2215 O Me 252.318 253.54 2216 OtBu 294.399 295.51 2217 O Ch 320.437 321.57 2218 nHex O iBu 336.48 337.6  2219 O iPr 322.453 323.56 2220 O Ph 356.47  357.12 2221 O Me294.399 295.54 2222 O nBu 336.48  337.58 2223 O tBu 336.48  337.56 2224O Ch 362.518 363.64 2225 2226 2227 2228 2229

O O O O O iBu iPr Ph Me Ch 334.464 320.437 354.454 292.383 360.502335.58 321.55 354.87 293.53 361.6  2230 2231 2232 2233 2234 2235 2236

O O O O O O O iBu iPr Ph Me nBu tBu Ch 342.443 328.416 362.433 300.362342.443 342.443 368.481 343.55 329.53 363.16 301.51 343.52 343.53 369.612237 2238 2239 2240 2241 2242 2243

O O O O O O O iBu iPr Ph Me nBu tBu Ch 352.435 338.408 372.425 310.354352.435 352.435 378.473 353.57 339.51 373.12 311.51 353.53 353.52 379.572244

O tBu 356.426 357.49 2245 2246 2247 2248 2249 2250 2251

O O O O O O O iBu iPr Ph Me nBu tBu Ch 328.416 314.389 348.406 286.335328.416 328.416 354.454 329.54 315.49 349.1  287.52 329.5  329.5  354.872252 2253 2254 2255 2256 2257 2258

O O O O O O O iBu iPr Ph Me nBu tBu Ch 358.442 344.415 378.432 316.361358.442 358.442 384.48  359.58 345.48 379.1  317.52 359.51 359.5  385.592259 2260 2261 2262 2263 2264 2265

O O O O O O O iBu iPr Ph Me nBu tBu Ch 342.443 328.416 362.433 300.362342.443 342.443 368.481 343.56 329.51 363.1  301.5  343.56 343.52 369.582266 2267 2268 2269 2270 2271 2272

O O O O O O O iBu iPr Ph Me nBu tBu Ch 397.306 383.279 417.296 355.225397.306 397.306 423.344 397.51 383.46 417.06 355.42 397.46 397.45 423.462273 2274 2275 2276 2277 2278 2279

O O O O O O O iBu iPr Ph Me nBu tBu Ch 346.406 332.379 366.396 304.325346.406 346.406 372.444 347.55 333.47 367.11 305.5  347.53 347.5  373.562280 2281 2282 2283 2284 2285 2286

O O O O O O O iBu iPr Ph Me nBu tBu Ch 346.406 332.379 366.396 304.325346.406 346.406 372.444 347.54 333.47 367.15 305.49 347.5  347.46 373.562287 2288 2289 2290 2291 2292 2293

O O O O O O O iBu iPr Ph Me nBu tBu Ch 378.476 364.449 398.466 336.395378.476 378.476 404.514 379.59 365.52 399.13 337.49 379.55 379.5  405.542294 2295 2296 2297 2298 2299 2300

O O O O O O O iBu iPr Ph Me nBu tBu Ch 396.413 382.386 416.403 354.332396.413 396.413 422.451 397.55 383.52 417.13 355.47 397.5  397.48 423.5 2301 2302 2303 2304 2305 2306 2307

O O O O O O O iBu iPr Ph Me nBu tBu Ch 362.861 348.834 382.851 320.78 362.861 362.861 388.899 363.49 349.46 383.13 321.46 363.47 363.45 389.532308 2309 2310 2311 2312 2313 2314

O O O O O O O iBu iPr Ph Me nBu tBu Ch 362.861 348.834 382.851 320.78 362.861 362.861 388.899 363.52 349.44 383.16 321.46 363.47 363.48 389.562315 2316 2317 2318 2319 2320 2321

O O O O O O O iBu iPr Ph Me nBu tBu Ch 362.861 348.834 382.851 320.78 362.861 362.861 388.899 363.5  349.48 383.11 321.43 363.46 363.46 389.552322 2323 2324 2325 2326 2327 2328

O O O O O O O iBu iPr Ph Me nBu tBu Ch 358.442 344.415 378.432 316.361358.442 358.442 384.48  359.59 345.55 379.11 317.5  359.52 359.52 385.6 2329 2330 2331 2332 2333 2334

O O O O O O iBu iPr Ph Me nBu Ch 358.442 344.415 378.432 316.361 358.442384.48  359.55 345.49 379.16 317.5  359.52 385   2335 2336 2337 23382339 2340 2341

O O O O O O O iBu iPr Ph Me nBu tBu Ch 373.413 359.386 393.403 331.332373.413 373.413 399.451 374.57 360.5  394.21 332.47 374.52 374.44 400.562342 2343 2344 2345 2346 2347 2348

O O O O O O O iBu iPr Ph Me nBu tBu Ch 397.306 383.279 417.296 355.225397.306 397.306 423.344 397.47 383.44 417.1  355.49 397.46 397.42 423.412349 2350 2351 2352 2353 2354 2355

O O O O O O O iBu iPr Ph Me nBu tBu Ch 356.47  342.443 376.46  314.389356.47  356.47  382.508 357.58 343.53 377.14 315.55 357.54 357.52 383.582356 2357 2358 2359 2360 2361 2362

O O O O O O O iBu iPr Ph Me nBu tBu Ch 397.306 383.279 417.296 355.225397.306 397.306 423.344 397.48 383.43 417.04 355.43 397.43 397.44 423.442363 2364 2365 2366 2367 2368 2369

O O O O O O O iBu iPr Ph Me nBu tBu Ch 388.468 374.441 408.458 346.387388.468 388.468 414.506 389.6  375.57 409.19 347.52 388.95 389.55 415.582370 2371 2372 2373 2374 2375 2376

O O O O O O O iBu iPr Ph Me nBu tBu Ch 364.396 350.369 384.386 322.315364.396 364.396 390.434 365.54 351.48 385.09 323.49 365.51 365.49 391.572377 2378 2379 2380 2381 2382 2383

O O O O O O O iBu iPr Ph Me nBu tBu Ch 404.514 390.487 424.504 362.433404.514 404.514 430.552 405.58 391.56 425.17 363.53 405.56 405.55 431.572384 nPr S secBu 310.464 311.45 2385 S iPr 296.437 297.52 2386 S Ph330.454 331.11 2387 S tBu 310.464 311.45 2388 2389 2390 2391 2392 23932394

S S S S S S S iBu iPr Ph Me nBu tBu Ch 358.508 344.481 378.498 316.427358.508 358.508 384.546 359.55 345.47 379.13 317.47 359.5  359.5  385.242395 2396 2397 2398 2399 2400 2401

S S S S S S S iBu iPr Ph Me nBu tBu Ch 372.535 358.508 392.525 330.454372.535 372.535 398.573 373.6  359.49 393.17 331.5  373.59 373.51 399.612402 2403 2404 2405

S S S S iBu Ph tBu Ch 374.507 394.497 374.507 400.545 375.57 395.13375.51 401.53 2406 2407 2408 2409 2410 2411 2412

S S S S S S S iBu iPr Ph Me nBu tBu Ch 372.491 358.464 392.481 330.41 372.491 372.491 398.529 373.5  359.49 393.14 331.52 373.5  373.49 399.522413 2414 2415 2416 2417 2418

S S S S S S iBu iPr Ph Me tBu Ch 336.502 322.475 356.492 294.421 336.502362.54  337.58 323.43 357.11 295.51 337.52 363.6  2419 2420 2421 24222423

S S S S S iBu iPr Ph Me tBu 364.556 350.529 384.546 322.475 364.556365.6  351.46 385.24 323.49 345.49

TABLE 15

Example No R′ Z AA Mol Wt [M + H] + 2424 Et O Tic 326.4  327.54 2425 iPrO Tic 340.427 341.57 2426 O Pic 292.383 293.58 2427 O Oic 332.448 333.172428 nHex O Tic 382.508 383.58 2429 O Oic 374.529 375.38 2430 2431 2432

O O O Tic Pic Oic 380.492 332.448 372.513 381.62 333.53 373.21 2433 24342435

O O O Tic Pic Oic 388.471 340.427 380.492 389.59 341.57 381.26 2436 24372438

O O O Tic Pic Oic 398.463 350.419 390.484 399.56 351.56 391.26 2439 24402441

O O O Tic Pic Oic 374.444 326.4  366.465 375.53 327.5  368.04 2442 24432444

O O O Tic Pic Oic 404.47  356.426 396.491 405.52 357.51 397.24 2445 24462447

O O O Tic Pic Oic 388.471 340.427 380.492 389.6  341.52 381.3  2448 2449

O O Tic Oic 443.334 435.355 443.43 435.21 2450 2451 2452

O O O Tic Pic Oic 392.434 344.39  384.455 393.69 345.48 385.26 2453 24542455

O O O Tic Pic Oic 392.434 344.39  384.455 393.48 345.46 385.18 2456 2457

O O Tic Oic 424.504 416.525 425.49 417.31 2458 2459 2460

O O O Tic Pic Oic 442.441 394.397 434.462 443.48 395.52 435.25 2461 24622463

O O O Tic Pic Oic 408.889 360.845 400.91  409.48 361.4  401.24 2464 24652466

O O O Tic Pic Oic 408.889 360.845 400.91  409.5  361.43 401.23 2467 24682469

O O O Tic Pic Oic 408.889 360.845 400.91  409.47 361.4  401.17 2470 24712472

O O O Tic Pic Oic 404.47  356.426 396.491 405.54 357.52 397.24 2473 24742475

O O O Tic Pic Oic 404.47  356.426 396.491 405.55 357.52 397.25 2476 24772478

O O O Tic Pic Oic 419.441 371.397 411.462 420.48 372.44 412.26 2479

O Tic 443.334 443.41 2480 2481 2482

O O O Tic Pic Oic 402.498 354.454 394.519 403.53 355.53 395.28 2483 24842485

O O O Tic Pic Oic 443.334 395.29  435.355 443.43 395.46 435.16 2486 24872488

O O O Tic Pic Oic 434.496 386.452 426.517 435.51 387.55 427.25 2489

O Oic 402.445 403.27 2490 2491 2492

O O O Tic Pic Oic 450.542 402.498 442.563 451.59 403.57 443.22 2493 nPrS Pic 308.448 309.46 2494 S Oic 348.513 349.21 2495 2496

S S Pic Oic 356.492 396.557 357.47 397.24 2497 2498

S S Pic Oic 370.519 410.584 371.5  411.27 2499

S Oic 412.556 413.18 2500 2501

S S Tic Oic 418.519 410.54  419.49 411.2  2502 2503

S S Tic Oic 382.53  374.551 383.58 375.28 2504 2505 2506

S S S Tic Pic Oic 410.584 362.54  402.605 411.57 363.64 403.28

TABLE 16

Example No R′ Z R5 Mol Wt [M + H]+ 2507 Et O Ph 314.389 315.09 2508 O Ch320.437 321.51 2509 O OCH₂Ph 300.362 301.07 2510 O CH₂CO₂CH₂Ph 386.452387.18 2511 iPr O OCH₂Ph 314.389 315.03 2512 O CH₂CO₂CH₂Ph 400.479401.27 2513 nHex O Ph 370.497 371.33 2514 O Ch 376.545 377.66 2515 OOCH₂Ph 356.47  357.12 2516 O CH₂CO₂CH₂Ph 442.56  443.23 2517 O CO₂CH₃352.435 353.56 2518 2519 2520 2521 2522

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 368.481 374.529 354.454440.544 350.419 369.27 375.69 354.87 441.23 351.51 2523 2524 2525 25262527

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 376.46  382.508 362.433448.523 358.398 377.19 383.6  363.16 449.26 359.51 2528 2529 2530 25312532

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 386.452 392.5  372.425 458.515368.39  387.24 393.61 373.12 459.26 369.48 2533

O CH₂CO₂CH₂Ph 398.463 399.19 2534 2535 2536 2537 2538

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 362.433 368.481 348.406434.496 344.371 363.24 369.27 349.1  435.23 345.48 2539 2540 2541 25422543

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 392.459 398.507 378.432464.522 374.397 393.19 399.54 379.1  465.23 375.51 2544 2545 2546 25472548

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 376.46  382.508 362.433448.523 358.398 377.25 383.6  363.1  449.23 359.49 2549 2550 2551 25522553

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 431.323 437.371 417.296503.386 413.261 431.02 437.45 417.06 503.18 413.39 2554 2555 2556 25572558

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 380.423 386.471 366.396452.486 362.361 381.13 387.59 367.11 453.36 363.47 2559

O CH₂CO₂CH₂Ph 452.486 453.2 2560 2561 2562 2563

O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph 380.423 386.471 366.396 452.486 381.15387.57 367.15 453.17 2564 2565 2566 2567 2568

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 412.493 418.541 398.466484.556 394.431 413.21 419.55 399.13 485.24 395.52 2569 2570 2571 25722573

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 430.43  436.478 416.403502.493 412.368 431.04 437.51 417.13 503.23 413.46 2574 2575 2576 25772578

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 396.878 402.926 382.851468.941 378.816 397.24 403.53 383.13 469.16 378.84 2579 2580 2581 25822583

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 396.878 402.926 382.851468.941 378.816 397.12 403.46 383.16 469.2  379.47 2584 2585 2586 25872588

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 396.878 402.926 382.851468.941 378.816 397.11 403.51 383.11 469.11 379.48 2589 2590 2591 25922593

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 392.459 398.507 378.432464.522 374.397 393.2  399.58 379.11 465.25 375.49 2594 2595 2596 25972598

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 392.459 398.507 378.432464.522 374.397 393.25 399.54 379.16 465.23 375.51 2599 2600 2601 26022603

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 407.43  413.478 393.403479.493 389.368 408.19 414.54 394.21 480.25 390.48 2604 2605 2606 26072608

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 431.323 437.371 417.296503.386 413.261 431.01 437.43 417.1  503.15 413.37 2609 2610 2611 26122613

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 390.487 396.535 376.46 462.55  372.425 391.27 397.59 377.14 463.31 373.51 2614 2615 2616 2617

O O O O Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 437.371 417.296 503.386 413.261437.45 417.04 503.14 413.38 2618 2619 2620 2621 2622

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 422.485 428.533 408.458494.548 404.423 423.28 429.58 409.19 495.24 404.91 2623 2624 2625 26262627

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 398.413 404.461 384.386470.476 380.351 399.19 405.53 385.09 471.22 381.49 2628 2629 2630 26312632

O O O O O Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 438.531 444.579 424.504510.594 420.469 439.24 445.57 425.17 511.28 421.46 2633 nPr S Ph 344.481345.27 2634 S Ch 350.529 351.15 2635 S OCH₂Ph 330.454 331.11 2636 SCH₂CO₂CH₂Ph 416.544 417.25 2637 S CO₂CH₃ 326.419 327.24 2638 2639 26402641 2642

S S S S S Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 392.525 398.573 378.498464.588 374.463 393.28 399.53 379.13 465.18 375.44 2643 2644 2645 26462647

S S S S S Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 406.552 412.6  392.525 478.615388.49  407.3  413.53 393.17 479.25 389.48 2648 2649 2650 2651

S S S S Ph Ch OCH₂Ph CH₂CO₂CH₂Ph 408.524 414.572 394.497 480.587 409.21415.51 395.13 481.18 2652 2653 2654 2655 2656

S S S S S Ph Ch OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 406.508 412.556 392.481478.571 388.446 406.9  413.6  393.14 479.14 389.45 2657 2658 2659 2660

S S S S Ph OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 370.519 356.492 442.582 352.457371.04 357.11 443.17 353.46 2661 2662 2663 2664

S S S S Ph OCH₂Ph CH₂CO₂CH₂Ph CO₂CH₃ 398.573 384.546 470.636 380.511399.53 385.24 471.2  381.54

TABLE 17

Example No R′ Z n Mol Wt [M + H]+ 2665 Et O 1 387.44  388.27 2666 O 3415.494 416.24 2667 O 2 401.467 402.28 2668 O 4 429.521 430.25 2669 iPrO 1 401.467 402.26 2670 O 3 429.521 430.26 2671 O 2 415.494 416.27 2672O 4 443.548 444.23 2673 nHex O 1 443.548 444.31 2674 O 3 471.602 472.342675 O 2 457.575 458.32 2676 O 4 485.629 486.37 2677 2678 2679 2680

O O O O 1 3 2 4 441.532 469.586 455.559 483.613 442.29 470.27 456.31484.29 2681 2682 2683 2684

O O O O 1 3 2 4 449.511 477.565 463.538 491.592 450.24 478.31 464.33492.24 2685 2686 2687 2688

O O O O 1 3 2 4 459.503 487.557 473.53  501.584 460.31 488.24 474.33502.26 2689 2690

O O 1 2 463.494 477.521 464.22 478.23 2691 2692 2693 2694

O O O O 1 3 2 4 435.484 463.538 449.511 477.565 436.23 464.21 450.26478.3  2695 2696 2697 2698

O O O O 1 3 2 4 465.51  493.564 479.537 507.591 466.25 494.27 480.25508.22 2699 2700 2701 2702

O O O O 1 3 2 4 449.511 477.565 463.538 491.592 450.26 478.27 464.31492.23 2703 2704 2705 2706

O O O O 1 3 2 4 504.374 532.428 518.401 546.455 504.22 532.19 518.25546.24 2707 2708 2709 2710

O O O O 1 3 2 4 453.474 481.528 467.501 495.555 454.23 482.2  468.28496.21 2711 2712 2713

O O O 1 2 4 453.474 467.501 495.555 454.3  468.25 496.25 2714 2715 27162717

O O O O 1 3 2 4 453.474 481.528 467.501 495.555 454.23 482.23 468.24496.28 2718 2719 2720 2721

O O O O 1 3 2 4 485.544 513.598 499.571 527.625 486.22 514.29 500.26528.32 2722 2723 2724 2725

O O O O 1 3 2 4 503.481 531.535 517.508 545.562 504.27 532.24 518.26546.28 2726 2727 2728 2729

O O O O 1 3 2 4 469.929 497.983 483.956 512.01  470.19 498.27 484.18512.27 2730 2731 2732 2733

O O O O 1 3 2 4 469.929 497.983 483.956 512.01  470.19 498.23 484.26512.26 2734 2735 2736 2737

O O O O 1 3 2 4 469.929 497.983 483.956 512.01  470.27 498.21 484.26512.24 2738 2739 2740 2741

O O O O 1 3 2 4 465.51  493.564 479.537 507.591 466.24 494.4  480.32508.24 2742 2743 2744 2745

O O O O 1 3 2 4 465.51  493.564 479.537 507.591 466.26 494.23 480.26508.23 2746 2747 2748 2749

O O O O 1 3 2 4 480.481 508.535 494.508 522.562 481.22 509.3  495.28523.25 2750 2751 2752 2753

O O O O 1 3 2 4 504.374 532.428 518.401 546.455 504.17 532.18 518.19546.27 2754 2755 2756 2757

O O O O 1 3 2 4 463.538 491.592 477.565 505.619 464.25 492.27 478.28506.27 2758 2759 2760 2761

O O O O 1 3 2 4 504.374 532.428 518.401 546.455 504.23 532.13 518.2 546.24 2762 2763 2764 2765

O O O O 1 3 2 4 495.536 523.59  509.563 537.617 496.29 524.24 510.28538.3  2766 2767 2768 2769

O O O O 1 3 2 4 471.464 499.518 485.491 513.545 472.21 500.18 486.29514.27 2770 2771 2772 2773

O O O O 1 3 2 4 511.582 539.636 525.609 553.663 512.3  540.28 526.31554.35 2774 nPr S 1 417.532 418.23 2775 S 3 445.586 446.31 2776 S 2431.559 432.22 2777 S 4 459.613 460.25 2778 2779 2780 2781

S S S S 1 3 2 4 465.576 493.63  479.603 507.657 466.21 494.32 480.25508.23 2782 2783 2784 2785

S S S S 1 3 2 4 479.603 507.657 493.63  521.684 480.23 508.23 494.3 522.3  2786 2787 2788 2789

S S S S 1 3 2 4 481.575 509.629 495.602 523.656 482.21 510.26 496.22524.27 2790 2791 2792 2793

S S S S 1 3 2 4 479.559 507.613 493.586 521.64  480.23 508.21 494.25522.23

TABLE 18

Example No R′ Z R6 Mol Wt [M + H]+ 2794 Et O Me 252.318 253.51 2795 O H238.291 239.54 2796 iPr O Me 266.345 267.56 2797 nHex O Me 308.426309.55 2798 O H 294.399 295.58 2799 O secBu 350.507 351.41 2800 O CH₂Ph384.524 385.67 2801 2802 2803

O O O Me H CH₂Ph 306.41  292.383 382.508 307.53 293.46 383.59 2804 28052806

O O O H secBu CH₂Ph 300.362 356.47  390.487 301.49 357.3  391.56 28072808 2809

O O O Me H CH₂Ph 324.381 310.354 400.479 325.54 311.54 401.58 2810 2811

O O secBu CH₂Ph 370.453 404.47  371.32 405.46 2812 2813 2814 2815

O O O O Me H secBu CH₂Ph 300.362 286.335 342.443 376.46  301.55 287.5 343.32 377.53 2816 2817 2818 2819

O O O O Me H secBu CH₂Ph 330.388 316.361 372.469 406.486 331.55 317.51373.33 407.53 2820 2821 2822 2823

O O O O Me H secBu CH₂Ph 314.389 300.362 356.47  390.487 315.54 301.49357.31 391.55 2824 2825 2826 2827

O O O O Me H secBu CH₂Ph 369.252 355.225 411.333 445.35  369.41 355.42411.18 445.36 2828 2829 2830 2831

O O O O Me H secBu CH₂Ph 318.352 304.325 360.433 394.45  319.47 305.5 361.28 395.52 2832

O secBu 360.433 361.28 2833 2834

O O Me H 318.352 304.325 319.53 305.5  2835 2836 2837 2738

O O O O Me H secBu CH₂Ph 350.422 336.395 392.503 426.52  351.53 337.51393.35 427.5  2839 2840 2841 2842

O O O O Me H secBu CH₂Ph 368.359 354.332 410.44  444.457 369.57 355.46411.29 445.51 2843 2844 2845 2846

O O O O Me H secBu CH₂Ph 334.807 320.78  376.888 410.905 335.51 321.44377.24 411.51 2847 2848 2849 2850

O O O O Me H secBu CH₂Ph 334.807 320.78  376.888 410.905 335.53 321.47377.28 411.47 2851 2852 2853 2854

O O O O Me H secBu CH₂Ph 334.807 320.78  376.888 410.905 335.36 321.46377.22 411.46 2855 2856 2857 2858

O O O O Me H secBu CH₂Ph 330.388 316.361 372.469 406.486 331.5  317.48373.31 407.52 2859 2860 2861 2862

O O O O Me H secBu CH₂Ph 330.388 316.361 372.469 406.486 331.52 317.49373.33 407.51 2863 2864 2865 2866

O O O O Me H secBu CH₂Ph 345.359 331.332 387.44  421.457 346.46 332.48388.33 422.41 2867 2868 2869 2870

O O O O Me H secBu CH₂Ph 369.252 355.225 411.333 445.35  369.38 355.42411.12 445.33 2871 2872 2873 2874

O O O O Me H secBu CH₂Ph 328.416 314.389 370.497 404.514 329.53 315.51371.34 405.52 2875 2876 2877 2878

O O O O Me H secBu CH₂Ph 369.252 355.225 411.333 445.35  369.47 355.39411.26 445.39 2879 2880 2881 2882

O O O O Me H secBu CH₂Ph 360.414 346.387 402.495 436.512 361.38 347.54403.35 437.41 2883 2884 2885 2886

O O O O Me H secBu CH₂Ph 336.342 322.315 378.423 412.44  337.45 323.49379.25 413.51 2887 2888 2889 2890

O O O O Me H secBu CH₂Ph 376.46  362.433 418.541 452.558 377.53 363.51419.31 453.54 2891 nPr S Me 282.41  283.56 2892 S secBu 324.491 325.232893 2894 2895

S S S H secBu CH₂Ph 316.427 372.535 406.552 317.51 373.33 407.55 28962897 2898

S S S H secBu CH₂Ph 330.454 386.562 420.579 331.51 387.34 421.53 28992900

S S H secBu 330.41  386.518 331.46 387.3  2901 2902 2903

S S S Me H secBu 308.448 294.421 350.529 309.52 295.51 351.31 2904

S secBu 378.583 379.36

TABLE 19

Example No R R7 Moll Wt [M + H]+ 2905 CH₃ H 195.222 196.17 2906 secBu251.33  252.27 2907 CH₂Ph 285.347 286.24 2908 2909 2910 2911

H iPr secBu CH₂Ph 257.293 299.374 313.401 347.418 258.18 300.18 314.25348.22 2912 2913 2914 2915

H iPr secBu CH₂Ph 291.738 333.819 347.846 381.863 292.12 334.16 348.23382.25 2916 2917 2918 2919

H iPr secBu CH₂Ph 291.738 333.819 347.846 381.863 292.13 334.17 348.21382.21 2920 2921 2922 2923

H iPr secBu CH₂Ph 291.738 333.819 347.846 381.863 292.11 334.15 348.19382.22 2924 2925 2926 2927

H iPr secBu CH₂Ph 326.183 368.264 382.291 416.308 326.1  368.12 382.21416.15 2928 2929 2930 2931

H iPr secBu CH₂Ph 326.183 368.264 382.291 416.308 326.07 368.13 382.2 416.13 2932

iPr 368.264 368.13 2933 2934 2935 2936

H iPr secBu CH₂Ph 275.283 317.364 331.391 365.408 276.19 318.21 332.24366.24 2937 2938 2939 2940

H iPr secBu CH₂Ph 275.283 317.364 331.391 365.408 276.19 318.18 332.23366.26 2941 2942 2943 2944

H iPr secBu CH₂Ph 287.319 329.4  343.427 377.444 288.17 330.24 344.25378.29 2945 2946 2947 2948

H iPr secBu CH₂Ph 287.319 329.4  343.427 377.444 288.2  330.23 344.25378.26 2949

CH₂Ph 391.427 391.33 2950 2951 2952 2953

H iPr secBu CH₂Ph 271.32  313.401 327.428 361.445 272.19 314.2  328.24362.26 2954 2955 2956 2957

H iPr secBu CH₂Ph 271.32  313.401 327.428 361.445 272.16 314.22 328.28362.24 2958 2959 2960 2961

H iPr secBu CH₂Ph 271.32  313.401 327.428 361.445 272.21 314.22 328.26362.28 2962

secBu 338.411 339.07 2963 2964 2965 2966

H iPr secBu CH₂Ph 325.29  367.371 381.398 415.415 326.15 368.2  382.26416.21 2967 2968

H CH₂Ph 302.29  392.415 303.13 393.24 2969

H 282.303 284.13 2970 iPr 349.434 350.23 2971 SecBu 363.461 364.29 2972CH₂Ph 397.478 398.27 2973 2974 2975 2976

H iPr secBu CH₂Ph 307.353 349.434 363.461 397.478 308.18 350.23 364.26398.29 2977 2978 2979 2980

H iPr secBu CH₂Ph 313.401 355.482 369.509 403.526 314.21 356.26 370.33404.29 2981 2982 2983 2984

H iPr secBu CH₂Ph 275.283 317.364 331.391 365.408 276.15 318.21 332.24366.26 2985 2986 2987 2988

H iPr secBu CH₂Ph 326.183 368.264 382.291 416.308 326.12 368.13 382.18416.14 2989 2990 2991 2992

H iPr secBu CH₂Ph 325.29  367.371 381.398 415.415 326.19 368.19 382.25416.21 2993 2994 2995 2996

H iPr secBu CH₂Ph 336.194 378.275 392.302 426.319 336.0  378.14 392.19426.15 2997

iPr 329.4  330.25 2998 2999 3000 3001

H iPr secBu CH₂Ph 329.4  371.481 385.508 419.525 330.24 372.24 386.34420.28 3002 3003 3004 3005

H iPr secBu CH₂Ph 331.372 373.453 387.48  421.497 332.22 374.25 388.3 422.25 3006 3007 3008 3009

H iPr secBu CH₂Ph 341.455 383.536 397.563 431.58  343.45 384.33 398.35432.3  3010 3011 3012 3013

H iPr secBu CH₂Ph 271.32  313.401 327.428 361.445 272.18 314.2  328.29362.26 3014 3015 3016 3017

H iPr secBu CH₂Ph 285.347 327.428 341.455 375.472 286.21 328.25 342.32376.3  3018

iPr 355.46  356.15 3019 3020 3021 3022

H iPr secBu CH₂Ph 263.319 305.4  319.427 353.444 264.14 306.15 320.21354.22 3023 3024 3025 3026

H iPr secBu CH₂Ph 247.254 289.335 303.362 337.379 248.14 290.14 304.24338.21 3027 3028 3029 3030

H iPr secBu CH₂Ph 301.346 343.427 357.454 391.471 302.2  344.22 358.3 392.31 3031 3032 3033 3034

H iPr secBu CH₂Ph 263.341 305.422 319.449 353.466 264.19 306.2  320.32354.33 3035 3036 3037

H iPr CH₂Ph 249.314 291.395 339.439 250.18 292.19 340.25 3038 3039 30403041

H iPr secBu CH₂Ph 235.287 277.368 291.395 325.412 236.13 278.17 292.29326.26 3042 3043 3044 3045

H iPr secBu CH₂Ph 221.26  263.341 277.368 311.385 222.13 264.18 278.24312.23 3046 3047 3048 3049

H iPr secBu CH₂Ph 263.341 305.422 319.449 353.466 264.23 306.24 320.31354.3  3050 3051 3052 3053

H iPr secBu CH₂Ph 237.303 279.384 293.411 327.428 238.2  280.21 294.28328.29 3054

iPr 293.411 294.2  3055

iPr 293.411 294.2  3056 3057 3058

H iPr CH₂Ph 279.384 321.465 369.509 280.25 322.27 370.36 3059

iPr 309.366 310.2 3060

iPr 365.474 366.29 3061 3062 3063 3064

H iPr secBu CH₂Ph 297.358 339.439 353.466 387.483 298.18 340.23 354.3 388.28 3065 3066 3067 3068

H iPr secBu CH₂Ph 341.289 383.37  397.397 431.414 342.15 384.2  398.25432.16 3069 3070 3071 3072

H iPr secBu CH₂Ph 293.273 335.354 349.381 383.398 294.16 336.21 350.19384.22 3073 3074

H CH₂Ph 300.362 390.487 301.18 391.34 3075 3076 3077 3078

H iPr secBu CH₂Ph 315.417 357.498 371.525 405.542 316.26 358.27 372.32406.31 3079 3080 3081 3082

H iPr secBu CH₂Ph 311.263 353.344 367.371 401.388 312.13 354.17 368.24402.22 3083 3084 3085

H secBu CH₂Ph 277.346 333.454 367.471 278.15 334.24 368.23 3086 30873088 3089

H iPr secBu CH₂Ph 287.319 329.4  343.427 377.444 288.18 330.22 344.28378.27 3090 3091 3092 3093

H iPr secBu CH₂Ph 293.273 335.354 349.381 383.398 294.13 336.2  350.24384.22 3094 3095 3096 3097

H iPr secBu CH₂Ph 299.374 341.455 355.482 389.499 300.21 342.26 356.28390.3  3098 3099 3100 3101

H iPr secBu CH₂Ph 263.319 305.4  319.427 353.444 264.12 306.14 320.21354.19 3102 3103 3104 3105

H iPr secBu CH₂Ph 293.273 335.354 349.381 383.398 294.15 336.19 350.21384.22 3106

iPr 355.46 356.16 3107 3108 3109 3110

H iPr secBu CH₂Ph 293.273 335.354 349.381 383.398 294.16 336.17 350.27384.27

TABLE 20

Example No R R8  X   Y Mol Wt [M + H]+ 3111 CH₃ CH₂Ph  S  CH₂ 303.384304.27 3112 tBu  S  CH₂ 269.367 270.24 3113 iPr  S  CH₂ 255.34  256.263114 iPr CF₂  CH₂ 273.283 274.17 3115 iPr —CH═CH— 235.287 236.1  31163117 3118 3119 3120

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 365.455331.438 317.411 335.354 297.358 366.25 332.21 318.15 336.2  298.14 31213122 3123 3124

CH₂Ph iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 399.9  351.856369.799 331.803 401.29 352.2  370.16 332.16 3125 3126 3127 3128 3129

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 399.9 365.883 351.856 369.799 331.803 401.26 366.21 352.19 370.15 332.13 31303131 3132 3133 3134

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 399.9 365.883 351.856 369.799 331.803 401.26 366.2  352.26 370.18 332.16 31353136 3137 3138

CH₂Ph iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 434.345 386.301404.244 366.248 435.33 386.11 404.12 366.1  3139 3140 3141 3142 3143

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 434.345400.328 386.301 404.244 366.248 435.23 400.25 386.2  404.14 366.12 31443145

CH₂Ph iPr  S  CH₂  S  CH₂ 434.345 386.301 435.13 386.2  3146 3147 31483149 3150

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 383.445349.428 335.401 353.344 315.348 384.27 350.18 336.21 354.16 316.16 31513152 3153 3154

CH₂Ph iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 383.445 335.401353.344 315.348 384.25 336.24 354.23 316.17 3155 3156 3157 3158 3159

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 395.481361.464 347.437 365.38  327.384 396.26 362.25 348.25 366.21 328.2  31603161 3162 3163 3164

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 395.481361.464 347.437 365.38  327.384 396.26 362.21 348.23 366.22 328.19 3165

CH₂Ph  S  CH₂ 409.464 410.34 3166 3167 3168 3169 3170

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 379.482345.465 331.438 349.381 311.385 380.32 0  332.26 350.26 312.21 3171 31723173 3174 3175

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 379.482345.465 331.438 349.381 311.385 380.27 346.26 332.21 350.2  312.17 31763177 3178 3179 3180

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 379.482345.465 331.438 349.381 311.385 380.3  346.24 332.23 350.22 312.2  31813182

CH₂Ph iPr  S  CH₂ —CH═CH— 390.465 322.368 391.31 322.26 3183 3184 31853186

CH₂Ph iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 433.452 385.408403.351 365.355 434.16 386.23 404.15 366.18 3187 3188 3189 3190

CH₂Ph iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 410.452 362.408380.351 342.355 410.3  363.22 381.21 343.21 3191

CH₂Ph  S  CH₂ 390.465 391.23 3192 3193 3194 3195

CH₂Ph iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 415.515 367.471385.414 347.418 416.24 368.28 386.24 348.19 3196 3197 3198 3199 3200

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 415.515381.498 367.471 385.414 347.418 416.66 382.26 368.26 386.23 348.21 32013202 3203 3204 3205

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 421.563387.546 373.519 391.462 353.466 422.28 388.29 374.27 392.29 354.23 3206

CH₂Ph  S  CH₂ 441.553 443.9  3207 3208 3209

CH₂Ph iPr iPr  S  CH₂ CF₂  CH₂ —CH═CH— 383.445 353.344 315.348 384.27354.17 316.19 3210 3211 3212 3213 3214

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 434.345400.328 386.301 404.244 366.248 435.22 400.13 386.2  404.13 366.06 32153216 3217 3218 3219

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CH₂  CH₂ —CH═CH— 433.452399.435 385.408 403.351 365.355 434.19 400.26 386.24 404.17 366.15 32203221 3222 3223 3224

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 444.356410.339 396.312 414.255 376.259 445.14 410.09 396.15 414.09 376.12 3225

CH₂Ph  S  CH₂ 395.481 396.26 3226 3227 3228 3229

CH₂Ph iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 437.562 389.518407.461 369.465 438.3  390.29 408.26 370.25 3230

CH₂Ph  S  CH₂ 410.452 411.52 3231 3232 3233

CH₂Ph tBu iPr  S  CH₂  S  CH₂ CF₂  CH₂ 439.534 405.517 409.433 440.29406.26 410.23 3234 3235 3236 3237 3238

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 449.617415.6  401.573 419.516 381.52  450.34 416.32 402.3  420.25 382.29 32393240 3241 3242 3243

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 379.482345.465 331.438 349.381 311.385 380.28 346.24 332.23 350.2  312.18 32443245 3246 3247 3248

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 393.509359.492 345.465 363.408 325.412 394.31 360.23 346.27 364.21 326.23 3249

CH₂Ph  S  CH₂ 421.541 422.18 3250 3251 3252 3253 3254

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 371.481337.464 323.437 341.38  303.384 372.24 338.17 324.19 342.14 304.1  32553256 3257 3258 3259

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 355.416321.399 307.372 325.315 287.319 356.22 322.19 308.27 326.2  288.13 3260

CH₂Ph  S  CH₂ 400.888 401.19 3261 3262 3263 3264 3265

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 409.508375.491 361.464 379.407 341.411 410.23 376.29 362.26 380.25 342.21 32663267 3268 3269 3270

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 371.503337.486 323.459 341.402 303.406 372.32 338.16 324.25 342.22 304.21 32713272

CH₂Ph iPr  S  CH₂ —CH═CH— 357.476 289.379 358.27 290.24 3273 3274 32753276 3277

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 343.449309.432 295.405 313.348 275.352 344.27 310.34   314.19 276.2  3278 32793280 3281 3282

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 329.422295.405 281.378 299.321 261.325 330.23 296.24 282.25 300.18 262.15 32833284 3285 3286 3287

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 371.503337.486 323.459 341.402 303.406 372.32 338.29 324.28 342.25 304.19 32883289 3290 3291 3292

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 345.465311.448 297.421 315.364 277.368 346.29 312.23 298.23 316.22 278.22 3293

CH₂Ph  S  CH₂ 359.492 360.29 3294

CH₂Ph  S  CH₂ 359.492 360.3  3295 3296 3297 3298 3299

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 387.546353.529 339.502 357.445 319.449 388.35 354.32 340.36 358.29 320.27 3300

CH₂Ph  S  CH₂ 375.447 376.25 3301

CH₂Ph  S  CH₂ 431.555 432.31 3302 3303 3304 3305 3306

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 405.52 371.503 357.476 375.419 337.423 406.26 372.24 358.25 376.24 338.21 33073308 3309 3310 3311

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 449.451415.434 401.407 419.35  381.354 450.25 416.19 402.23 420.19 382.17 33123313 3314 3315 3316

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 401.435367.418 353.391 371.334 333.338 402.22 368.18 354.22 372.19 334.14 33173318 3319 3320

CH₂Ph tBu iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ 408.524 374.507360.48  378.423 409.29 375.28 361.28 379.27 3321

CH₂Ph  S  CH₂ 366.443 367.24 3322 3323 3324 3325

CH₂Ph tBu iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 423.579 389.562393.478 355.482 424.3  390.31 394.3  356.25 3326 3327 3328 3329 3330

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 419.425385.408 371.381 389.324 351.328 420.17 385.24 372.2  390.22 352.15 33313332 3333 3334 3335

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 385.508351.491 337.464 355.407 317.411 386.26 352.23 338.25 356.18 318.15 33363337 3338 3339 3340

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 395.481361.464 347.437 365.38  327.384 396.28 362.29 348.24 366.19 328.22 33413342 3343 3344 3345

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 401.435367.418 353.391 371.334 333.338 402.23 368.29 354.17 372.16 334.21 33463347 3348 3349 3350

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 407.536373.519 359.492 377.435 339.439 408.25 374.29 360.28 378.27 340.23 33513352 3353 3354 3355

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 371.481337.464 323.437 341.38  303.384 372.2  338.16 324.13 342.16 304.1  33563357 3358 3359 3360

CH₂Ph tBu iPr iPr iPr  S  CH₂  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 401.435367.418 353.391 371.334 333.338 402.24 368.3  354.15 372.18 334.16 3361

CH₂Ph  S  CH₂ 421.541 422.22 3362 3363 3364 3365

tBu iPr iPr iPr  S  CH₂  S  CH₂ CF₂  CH₂ —CH═CH— 367.418 353.391 371.334333.338 368.27 354.2  372.24 334.23

TABLE 21

Example No R′ Z R9 Mol Wt [M + H]+ 3366 Et O H 224.264 225.13 3367 OCH₂Ph 314.389 315.25 3368 iPr O H 238.291 239.21 3369 O CH₂Ph 328.416329.26 3370 O secBu 294.399 295.27 3371 nHex O H 280.372 281.3 3372 OCH₂Ph 370.497 371.31 3373 3374 3375

O O O H CH₂Ph secBu 278.356 368.481 334.464 279.28 369.32 335.31 33763377 3378

O O O H CH₂Ph secBu 286.335 376.46 342.443 287.23 377.26 343.26 33793380

O O H CH₂Ph 296.327 386.452 297.23 387.29 3381 3382

O O H CH₂Ph 300.318 390.443 301.19 391.26 3383 3384 3385

O O O H CH₂Ph secBu 272.308 362.433 328.416 273.22 363.23 329.25 33863387

O O H CH₂Ph 302.334 392.459 303.23 393.27 3388 3389 3390

O O O H CH₂Ph secBu 286.335 376.46 342.443 287.25 377.29 343.29 33913392

O O H CH₂Ph 341.198 431.323 341.14 431.15 3393 3394 3395

O O O H CH₂Ph secBu 290.298 380.423 346.406 291.22 381.25 347.22 33963397

O O H CH₂Ph 290.298 380.423 291.21 381.26 3398 3399

O O H CH₂Ph 290.298 380.423 291.19 381.26 3400 3401 3402

O O O H CH₂Ph secBu 322.368 412.493 378.476 323.22 413.24 379.33 34033404 3405

O O O H CH₂Ph secBu 340.305 430.43 396.413 341.23 431.2 397.24 3406 34073408

O O O H CH₂Ph secBu 306.753 396.878 362.861 307.16 397.23 363.26 34093410 3411

O O O H CH₂Ph secBu 306.753 396.878 362.861 307.16 397.22 363.21 34123413 3414

O O O H CH₂Ph secBu 306.753 396.878 362.861 307.18 397.21 363.21 34153416 3417

O O O H CH₂Ph secBu 302.334 392.459 358.442 303.2 393.28 359.28 34183419

O O H CH₂Ph 302.334 392.459 303.21 393.31 3420 3421 3422

O O O H CH₂Ph secBu 317.305 407.43 373.413 318.21 408.23 374.26 34233424

O O H CH₂Ph 341.198 431.323 341.14 431.15 3425 3426

O O H CH₂Ph 300.362 390.487 301.24 391.3 3427 3428

O O H CH₂Ph 341.198 431.323 341.17 431.15 3429 3430

O O H CH₂Ph 332.36 422.485 333.25 423.23 3431 3432

O O H CH₂Ph 308.288 398.413 309.17 399.24 3433 3434 3435

O O O H CH₂Ph secBu 348.406 438.531 404.514 349.26 439.25 405.29 3436nPr S H 254.356 255.23 3437

S H 302.4 303.21 3438

S H 316.427 317.21 3439

S H 318.399 319.22 3440 3441

S S H CH₂Ph 316.383 406.508 317.16 407.19 3442 3443 3444

S S S H CH₂Ph secBu 280.394 370.519 336.502 281.23 371.25 337.26 34453446

S S H CH₂Ph 308.448 398.573 309.23 399.31

TABLE 22

Example No R′ Z R10 X Y Mol Wt [M + H]+ 3447 Et O iPr S CH₂ 284.382285.24 3448 O tBu S CH₂ 298.409 299.26 3449 O iPr CH═CH 264.329 265.253450 iPr O iPr S CH₂ 298.409 299.25 3451 O iPr CF₂ CH₂ 316.352 317.223452 O tBu S CH₂ 312.436 313.26 3453 O iPr CH═CH 278.356 279.25 3454nHex O iPr S CH₂ 340.49 341.31 3455 O iPr CF₂ CH₂ 358.433 359.28 3456 OtBu S CH₂ 354.517 355.33 3457 O iPr CH═CH 320.437 321.28 3458 3459 34603461

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 338.474 356.417352.501 318.421 339.27 357.28 353.31 319.26 3462 3463 3464 3465

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 346.453 364.396360.48 326.4 347.25 365.27 361.29 327.26 3466 3467 3468 3469

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 356.445 374.388370.472 336.392 357.28 375.26 371.3 337.25 3470 3471

O O iPr iPr CF₂  CH₂ CH═CH 378.379 340.383 379.23 341.22 3472 3473 34743475

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 332.426 350.369346.453 312.373 333.23 351.22 347.26 313.21 3476 3477 3478 3479

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 362.452 380.395376.479 342.399 363.25 381.23 377.28 343.22 3480 3481 3482 3483

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 346.453 364.396360.48 326.4 347.24 365.23 361.29 327.25 3484 3485 3486 3487

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 401.316 419.259415.343 381.263 401.17 419.14 415.17 381.17 3488 3489 3490 3491

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 350.416 368.359364.443 330.363 351.23 369.24 365.25 331.2 3492 3493 3494 3495

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 350.416 368.359364.443 330.363 351.23 369.2 365.26 331.25 3496 3497 3498 3499

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 350.416 368.359364.443 330.363 351.24 369.24 365.25 331.23 3500 3501 3502 3503

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 382.486 400.429396.513 362.433 383.28 401.24 397.29 363.26 3504 3505 3506 3507

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 400.423 418.366414.45 380.37 401.24 419.19 415.24 381.23 3508 3509 3510 3511

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 366.871 384.814380.898 346.818 367.21 385.21 381.24 347.2 3512 3513 3514 3515

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 366.871 384.814380.898 346.818 367.21 385.2 381.24 347.19 3516 3517 3518 3519

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 366.871 384.814380.898 346.818 367.2 385.2 381.23 347.18 3520 3521 3522 3523

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 362.452 380.395376.479 342.399 363.26 381.25 377.28 343.25 3524 3525 3526

O O O iPr tBu iPr  S  CH₂  S  CH_(s) CH═CH 362.452 376.479 342.399363.27 377.27 343.27 3527 3528 3529 3530

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 377.423 395.366391.45 357.37 378.25 396.23 392.26 358.25 3531 3532 3533 3534

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 401.316 419.259415.343 381.263 401.15 419.12 415.16 381.14 3535 3536 3537 3538

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 360.48 378.423374.507 340.427 361.28 379.28 375.3 341.25 3539 3540 3541 3542

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 401.316 419.259415.343 381.263 401.2 419.13 415.15 381.18 3543 3544 3545 3546

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 392.478 410.421406.505 372.425 393.28 411.23 407.29 373.26 3547 3548 3549 3550

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 368.406 386.349382.433 348.353 369.25 387.22 383.26 349.19 3551 3552 3553 3554

O O O O iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 408.524 426.467422.551 388.471 409.27 427.22 423.27 389.28 3555 nPr S iPr S CH₂ 314.474315.22 3556 S iPr CF₂ CH₂ 332.417 333.2 3557 S tBu S CH₂ 328.501 329.273558 S iPr CH═CH 294.421 295.19 3559 3560 3561 3562

S S S S iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 362.518 380.461376.545 342.465 363.26 381.23 377.26 343.22 3563 3564 3565 3566

S S S S iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 376.545 394.488390.572 356.492 377.27 395.25 391.29 357.23 3567 3568 3569 3570

S S S S iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 378.517 396.46392.544 358.464 379.28 397.22 393.27 359.22 3571 3572 3573 3574

S S S S iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 376.501 394.444390.528 356.448 377.21 395.2 391.26 357.2 3575 3576 3577 3578

S S S S iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 340.512 358.455354.539 320.459 341.25 359.24 355.26 321.22 3579 3580 3581 3582

S S S S iPr iPr tBu iPr  S  CH₂ CF₂  CH₂  S  CH₂ CH═CH 368.566 386.509382.593 348.513 369.29 387.28 383.32 349.24

TABLE 23

Example No R R11 Mol Wt [M + H]+ 3583 CH₃ (CH₂)₄NHCOCH₃ 308.382 309.223584 C(CH₃)₂SCH₂NHCOCH₃ 340.446 341.22 3585 3586 3587 3588

(CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃ 371.441357.414 328.372 402.517 372.26 358.25 329.29 403.25 3589 3590 3591 3592

(CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃ 405.886391.859 362.817 436.962 406.2 392.19 363.21 437.2 3593 3594 3595 3596

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 404.898405.886 391.859 436.962 405.21 406.23 392.19 437.21 3597 3598 3599 36003601

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃404.898 405.886 391.859 362.817 436.962 405.21 406.22 392.22 363.18437.18 3602 3603 3604

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 439.343 440.331 471.407439.18 440.21 471.17 3605 3606 3607 3608 3609

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃439.343 440.331 426.304 397.262 471.407 439.17 440.18 426.16 397.16471.16 3610 3611 3612 3613

(CH₂)₄NHCOCH₃ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃ 439.343426.304 397.262 471.407 439.18 426.14 397.19 471.18 3614 3615 3616 3617

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 388.443389.431 375.404 420.507 389.25 390.26 376.22 421.24 3618 3619 3620 3621

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 388.443389.431 375.404 420.507 389.25 390.24 376.23 421.21 3622 3623 3624 36253626

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃400.479 401.467 387.44 358.398 432.543 401.26 402.27 388.25 359.23433.24 3627 3628 3629 3630 3631

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃400.479 401.467 387.44 358.398 432.543 401.26 402.29 388.27 359.25433.24 3632 3633

(CH₂)₄NHCOCH₃ C(CH₃)₂SCH₂NHCOCH₃ 384.48 416.544 385.28 417.22 3634 36353636 3637 3638

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃384.48 385.468 371.441 342.399 416.544 385.28 386.26 372.29 343.26417.24 3639 3640 3641 3642 3643

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃384.48 385.468 371.441 342.399 416.544 385.27 386.28 372.24 343.26417.25 3644

C(CH₃)₂SCH₂NHCOCH₃ 427.527 428.23 3645 3646 3647 3648

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 438.45439.438 425.411 470.514 439.25 440.25 426.21 471.24 3649 3650 3651 36523653

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃420.513 421.501 407.474 378.432 452.577 421.25 422.27 408.25 379.23453.29 3654 3655 3656 3657 3658

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃420.513 421.501 407.474 378.432 452.577 421.25 422.3 408.24 379.25453.26 3659 3660 3661 3662 3663

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃426.561 427.549 413.522 384.48 458.625 427.33 428.31 414.3 385.31 459.343664 3665 3666 3667 3668

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃388.443 389.431 375.404 346.362 420.507 389.27 390.26 376.22 347.24421.21 3669 3670 3671 3672 3673

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃439.343 440.331 426.304 397.262 471.407 439.18 440.19 426.15 397.14471.16 3674 3675 3676 3677 3678

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃438.45 439.438 425.411 396.369 470.514 439.24 440.25 426.21 397.21471.23 3679 3680 3681 3682 3683

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃449.354 450.342 436.315 407.273 481.418 449.17 450.21 436.14 407.15481.13 3684 3685 3686 3687 3688

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃400.479 401.467 387.44 358.398 432.543 401.26 402.29 388.23 359.22433.23 3689 3690 3691 3692 3693

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃442.56 443.548 429.521 400.479 474.624 443.32 444.36 430.27 401.27475.28 3694 3695 3696 3697 3698

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃444.532 445.52 431.493 402.451 476.596 445.29 446.3 432.27 404.24 477.283699 3700 3701 3702 3703

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃454.615 455.603 441.576 412.534 486.679 455.37 456.38 442.33 413.34487.33 3704 3705 3706 3707 3708

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃384.48 385.468 371.441 342.399 416.544 385.26 386.29 372.23 343.25417.24 3709 3710 3711 3712 3713

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃398.507 399.495 385.468 356.426 430.571 399.29 400.31 386.28 357.24431.26 3714 3715

(CH₂)₄NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 427.527 458.603 428.21 459.25 3716 37173718 3719 3720

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃376.479 377.467 363.44 334.398 408.543 377.23 378.21 364.2 335.26 409.23721 3722 3723 3724 3725

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃360.414 361.402 347.375 318.333 392.478 361.24 362.21 348.24 319.25393.21 3726

(CH₂)₂CONH₂ 363.805 364.16 3727 3728 3729 3730 3731

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃414.506 415.494 401.467 372.425 446.57 415.27 416.3 402.25 373.24 447.283732 3733 3734 3735 3736

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃376.501 377.489 363.462 334.42 408.565 377.3 378.34 364.29 335.26 409.263737 3738 3739 3740 3741

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃362.474 363.462 349.435 320.393 394.538 363.28 364.29 350.25 321.25395.28 3742 3743 3744 3745 3746

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃348.447 349.435 335.408 306.366 380.511 349.26 350.29 336.25 307.23381.23 3747 3748 3749 3750 3751

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃334.42 335.408 321.381 292.339 366.484 335.27 336.27 322.24 293.21367.21 3752 3753 3754 3755

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃ 376.501377.489 334.42 408.565 377.3 378.3 335.29 409.26 3756 3757 3758 37593760

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃350.463 351.451 337.424 308.382 382.527 351.28 352.29 338.26 309.24383.27 3761 3762 3763

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 364.49 365.478 396.554365.3 366.34 397.28 3764 3765 3766 3767 3768

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃364.49 365.478 351.451 322.409 396.554 365.31 366.32 352.29 323.32397.28 3769 3770 3771 3772 3773

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃392.544 393.532 379.505 350.463 424.608 393.33 394.37 380.31 351.3 425.33774 3775 3776 3777

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 380.445381.433 367.406 412.509 381.28 382.26 368.26 413.23 3778 3779 3780 37813782

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃436.553 437.541 423.514 394.472 468.617 437.34 438.33 424.28 395.32469.33 3783 3784 3785 3786 3787

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃410.518 411.506 397.479 368.437 442.582 411.27 412.29 398.26 369.28443.28 3788 3789 3790 3791 3792

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃454.449 455.437 441.41 412.368 486.513 455.25 456.28 442.23 413.2 487.213793 3794 3795 3796 3797

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃406.433 407.421 393.394 364.352 438.497 407.22 408.27 394.2 365.2 439.233798 3799 3800 3801 3802

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃413.522 414.51 400.483 371.441 445.586 414.3 415.31 401.27 372.28 446.293803 3804

(CH₂)₄NHCOCH₃ C(CH₃)₂SCH₂NHCOCH₃ 371.441 403.505 372.27 404.22 3805 38063807 3808 3809

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃428.577 429.565 415.538 386.496 460.641 429.33 430.32 416.32 387.33461.33 3810 3811 3812 3813 3814

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃424.423 425.411 411.384 382.342 456.487 425.23 426.23 412.21 383.23457.22 3815 3816 3817 3818

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 400.479401.467 387.44 432.543 401.26 402.29 388.25 433.25 3819 3820 3821 3822

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 406.433407.421 393.394 438.497 407.24 408.23 394.21 439.24 3823 3824 3825 38263827

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃412.534 413.522 399.495 370.453 444.598 413.3 414.27 400.27 371.31445.31 3828 3829 3830 3831

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ C(CH₃)₂SCH₂NHCOCH₃ 376.479377.467 363.44 408.543 377.21 378.25 364.19 409.18 3832 3833 3834 38353836

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃406.433 407.421 393.394 364.352 438.497 407.23 408.23 394.22 365.18439.21 3837 3838 3839 3840

(CH₂)₄NHCONH₂ (CH₂)₃NHCONH₂ (CH₂)₂CONH₂ C(CH₃)₂SCH₂NHCOCH₃ 427.527 413.5384.458 458.603 428.25 414.17 385.22 459.24 3841 3842

(CH₂)₄NHCOCH₃ (CH₂)₄NHCONH₂ 406.433 407.421 407.22 408.27

TABLE 24

Example No R X Mol Wt [M + H]+ 3843 CH₃ CH₂ 226.32 227.23 3844 CF₂ 262.3263.27 3845 3846 3847

CH₂ S CF₂ 288.391 306.428 324.371 289.29 307.25 325.28 3848 3849 3850

CH₂ S CF₂ 322.836 340.873 358.816 323.25 341.22 359.22 3851 3852 3853

CH₂ S CF₂ 322.836 340.873 358.816 323.24 341.21 359.23 3854 3855 3856

CH₂ S CF₂ 322.836 340.873 358.816 323.24 341.21 359.24 3857 3858 3859

CH₂ S CF₂ 357.281 375.318 393.261 357.21 375.22 393.18 3860 3861 3862

CH₂ S CF₂ 357.281 375.318 393.261 357.21 375.17 393.23 3863 3864 3865

CH₂ S CF₂ 357.281 375.318 393.261 357.23 375.17 393.22 3866 3867 3868

CH₂ S CF₂ 306.381 324.418 342.361 307.27 325.24 343.27 3869 3870 3871

CH₂ S CF₂ 306.381 324.418 342.361 307.28 325.26 343.28 3872 3873 3874

CH₂ S CF₂ 318.417 336.454 354.397 319.29 337.28 355.3 3875 3876 3877

CH₂ S CF₂ 318.417 336.454 354.397 319.3 337.25 355.29 3878 3879 3880

CH₂ S CF₂ 302.418 320.455 338.398 303.29 321.28 339.3 3881 3882 3883

CH₂ S CF₂ 302.418 320.455 338.398 303.3 321.26 339.29 3884 3885 3886

CH₂ S CF₂ 302.418 320.455 338.398 303.31 321.27 339.28 3887

CH₂ 313.401 314.28 3888 3889 3890

CH₂ S CF₂ 356.388 374.425 392.368 357.3 375.26 393.27 3891

S 351.425 353.45 3892 3893 3894

CH₂ S CF₂ 338.451 356.488 374.431 339.31 357.25 375.33 3895 3896 3897

CH₂ S CF₂ 338.451 356.488 374.431 339.31 357.25 375.3 3898 3899 3900

CH₂ S CF₂ 344.499 362.536 380.479 345.36 363.32 381.36 3901

S 382.526 384.3 3902 3903 3904

CH₂ S CF₂ 306.381 324.418 342.361 307.29 325.25 343.29 3905 3906 3907

CH₂ S CF₂ 357.281 375.318 393.261 357.23 375.18 393.22 3908 3909 3910

CH₂ S CF₂ 356.388 374.425 392.368 357.28 375.29 393.3 3911 3912 3913

CH₂ S CF₂ 367.292 385.329 403.272 367.22 385.19 403.17 3914

S 336.454 337.26 3915 3916 3917

CH₂ S CF₂ 360.498 378.535 396.478 361.36 379.34 397.37 3918 3919 3920

CH₂ S CF₂ 333.388 351.425 369.368 334.3 352.17 370.25 3921 3922 3923

CH₂ S CF₂ 362.47 380.507 398.45 363.33 381.31 399.32 3924 3925 3926

CH₂ S CF₂ 372.553 390.59 408.533 373.38 391.4 409.38 3927 3928 3929

CH₂ S CF₂ 302.418 320.455 338.398 303.32 321.25 339.28 3930 3931 3932

CH₂ S CF₂ 316.445 334.482 352.425 317.33 335.25 353.32 3933 3934

S CF₂ 362.514 380.457 363.22 381.28 3935 3936 3937

CH₂ S CF₂ 294.417 312.454 330.397 295.26 313.21 331.24 3938 3939 3940

CH₂ S CF₂ 278.352 296.389 314.332 279.28 297.27 315.21 3941 3942 3943

CH₂ S CF₂ 323.824 341.861 359.804 324.25 342.17 360.29 3944 3945 3946

CH₂ S CF₂ 332.444 350.481 368.424 333.32 351.29 369.32 3947 3948 3949

CH₂ S CF₂ 294.439 312.476 330.419 295.33 313.27 331.33 3950 3951 3952

CH₂ S CF₂ 280.412 298.449 316.392 281.34 299.3 317.32 3953 3954 3955

CH₂ S CF₂ 266.385 284.422 302.365 267.32 285.26 303.26 3956 3957

CH₂ CF₂ 252.358 288.338 253.31 289.3 3958 3959 3960

CH₂ S CF₂ 294.439 312.476 330.419 295.33 313.28 331.32 3961 3962

CH₂ CF₂ 268.401 304.381 269.33 305.27 3963 3964 3965

CH₂ S CF₂ 282.428 300.465 318.408 283.35 301.27 319.32 3966 3967 3968

CH₂ S CF₂ 282.428 300.465 318.408 283.35 301.3 319.32 3969 3970 3971

CH₂ S CF₂ 310.482 328.519 346.462 311.35 329.33 347.35 3972 3973 3974

CH₂ S CF₂ 298.383 316.42 334.363 299.3 317.26 335.27 3975 3976 3977

CH₂ S CF₂ 354.491 372.528 390.471 355.36 373.33 391.37 3978 3979 3980

CH₂ S CF₂ 328.456 346.493 364.436 329.33 347.28 365.33 3981 3982 3983

CH₂ S CF₂ 372.387 390.424 408.367 373.3 391.26 409.25 3984 3985 3986

CH₂ S CF₂ 324.371 342.408 360.351 325.28 343.25 361.25 3987 3988 3989

CH₂ S CF₂ 331.46 349.497 367.44 332.34 350.32 368.34 3990 3991 3992

CH₂ S CF₂ 289.379 307.416 325.359 290.29 308.23 326.27 3993 3994

CH₂ CF₂ 289.379 325.359 331.32 326.29 3995 3996 3997

CH₂ S CF₂ 346.515 364.552 382.495 347.38 365.33 383.37 3998 3999 4000

CH₂ S CF₂ 342.361 360.398 378.341 343.25 361.21 379.3 4001 4002 4003

CH₂ S CF₂ 318.417 336.454 354.397 319.31 337.28 355.3 4004 4005 4006

CH₂ S CF₂ 324.371 342.408 360.351 325.28 343.21 361.27 4007 4008 4009

CH₂ S CF₂ 330.472 348.509 366.452 331.35 349.31 367.36 4010 4011 4012

CH₂ S CF₂ 294.417 312.454 330.397 295.26 313.24 331.24 4013 4014 4015

CH₂ S CF₂ 324.371 342.408 360.351 325.28 343.24 361.26 4016 4017 4018

CH₂ S CF₂ 344.477 362.514 380.457 345.26 363.23 381.27 4019 4020 4021

CH₂ S CF₂ 324.371 342.408 360.351 325.27 343.25 361.3

TABLE 25

Example No R′ Z X Mol Wt [M + H]+ 4022 Et O CH₂ 255.362 256.31 4023 O S273.399 274.29 4024 O CF₂ 291.342 292.19 4025 iPr O CH₂ 269.389 270.364026 O S 287.426 288.29 4027 O CF₂ 305.369 306.23 4028 nHex O CH₂ 311.47312.37 4029 O S 329.507 330.34 4030 O CF₂ 347.45 348.31 4031 4032 4033

O O O CH₂ S CF₂ 309.454 327.491 345.434 310.37 328.31 346.3 4034 4035

O O CH₂ CF₂ 317.433 353.413 318.3 354.25 4036 4037 4038

O O O CH₂ S CF₂ 327.425 345.462 363.405 328.34 346.29 364.26 4039

O CH₂ 331.416 332.24 4040 4041 4042

O O O CH₂ S CF₂ 303.406 321.443 339.386 304.31 322.26 340.25 4043 40444045

O O O CH₂ S CF₂ 333.432 351.469 369.412 334.31 352.29 370.26 4046 40474048

O O O CH₂ S CF₂ 317.433 335.47 353.413 318.32 336.28 354.28 4049 40504051

O O O CH₂ S CF₂ 372.296 390.333 408.276 372.25 390.21 408.19 4052 40534054

O O O CH₂ S CF₂ 321.396 339.433 357.376 322.31 340.26 358.22 4055 40564057

O O O CH₂ S CF₂ 321.396 339.433 357.376 322.3 340.26 358.22 4058 40594060

O O O CH₂ S CF₂ 321.396 339.433 357.376 322.3 340.27 358.22 4061 40624063

O O O CH₂ S CF₂ 353.466 371.503 389.446 354.32 372.3 390.3 4064 40654066

O O O CH₂ S CF₂ 371.403 389.44 407.383 372.32 390.26 408.26 4067 40684069

O O O CH₂ S CF₂ 337.851 355.888 373.831 338.27 356.24 374.23 4070 40714072

O O O CH₂ S CF₂ 337.851 355.888 373.831 338.28 356.24 374.22 4073 40744075

O O O CH₂ S CF₂ 337.851 355.888 373.831 338.27 356.23 374.2 4076 40774078

O O O CH₂ S CF₂ 333.432 351.469 369.412 334.32 352.29 370.27 4079 40804081

O O O CH₂ S CF₂ 333.432 351.469 369.412 334.33 352.3 370.26 4082 40834084

O O O CH₂ S CF₂ 348.403 366.44 384.383 349.3 367.27 385.25 4085 40864087

O O O CH₂ S CF₂ 372.296 390.333 408.276 372.25 390.23 408.21 4088 40894090

O O O CH₂ S CF₂ 331.46 349.497 367.44 332.35 350.3 368.29 4091 4092 4093

O O O CH₂ S CF₂ 372.296 390.333 408.276 372.26 390.22 408.2 4094 40954096

O O O CH₂ S CF₂ 363.458 381.495 399.438 364.34 382.32 400.3 4097 40984099

O O O CH₂ S CF₂ 339.386 357.423 375.366 340.3 358.26 376.23 4100 41014102

O O O CH₂ S CF₂ 379.504 397.541 415.484 380.38 398.32 416.3 4103 nPr SCH₂ 285.454 286.29 4104 S S 303.491 304.31 4105 4106

S S CH₂ CF₂ 333.498 369.478 334.3 370.24 4107 4108

S S CH₂ CF₂ 347.525 383.505 348.3 384.25 4109 4110 4111

S S S CH₂ S CF₂ 349.497 367.534 385.477 350.27 368.2 386.27 4112 41134114

S S S CH₂ S CF₂ 347.481 365.518 383.461 348.3 366.23 384.2 4115 4116

S S S CF₂ 329.529 347.472 330.27 348.27 4117 4118 4119

S S S CH₂ S CF₂ 339.546 357.583 375.526 340.35 358.29 376.3

1. A compound according to general formula 1, or a compound which is atautomer or a stereoisomer thereof, or a pharmaceutically acceptablesalt of any of these,

wherein: X is selected among CH₂, S, CF₂, CHF, S(O), SO₂, CH₂CH₂ and acovalent bond, and Y is CH₂; or X and Y are together CH═CH; Q isselected among CN, H, B(OH)₂ and COX¹; X¹ is selected among H, alkyl,alkenyl, fluoroalkyl, aryl, heteroaryl, aryl (C₁-C₄) alkyl, heteroaryl(C₁-C₄) alkyl, CH₂NR⁴R⁵ and CH₂OR⁶; Z is selected among O and S; when Zis oxygen, R is selected from H, alkyl, alkenyl, aryl, heteroaryl, aryl(C₁-C₄) alkyl, heteroaryl (C₁-C₄) alkyl, arylO (C₁-C₄) alkyl, aryl(C₁-C₄) alkylO (C₁-C₄) alkyl, NR⁴R⁵, (C₁-C₄) alkyl CONR⁴R⁵ and (C₁-C₄)alkylCO₂R⁶; and when Z is sulphur, R is NR⁴R⁵; R¹ is selected among H,alkyl, alkenyl, aryl, heteroaryl, aryl (C₁-C₄) alkyl, heteroaryl (C₁-C₄)alkyl, (CH₂)_(a)NHW¹, (CH₂)_(b)COW², (CH₂)_(c)OW³, CH(Me)OW⁴,(CH₂)_(d)—C₆H₄—W⁵, C (Me)₂S(CH₂)_(e)NHW¹ and (CH₂)_(e)SW⁶; R² isselected among H and (C₁-C₄) alkyl; R³ is selected among H, alkyl,aryl(C₁-C₄)alkyl and —(CH₂)_(n)NH—C₅H₃N—W⁷; or R¹ and R³ are together—(CH₂)_(p)—; or R¹ and R² are together —(CH₂)_(q)—; or R¹ and R³together form a group according to the general formula 2 or generalformula 3

R⁴ and R⁵ are independently selected among H, alkyl, alkenyl, aryl,heteroaryl, aryl(C₁-C₄)alkyl and heteroaryl (C₁-C₄) alkyl; or R⁴ and R⁵are together —(CH₂)_(m)—; R⁶ is selected among H, alkyl, alkenyl, aryl,heteroaryl, aryl (C₁-C₄) alkyl, and heteroaryl (C₁-C₄) alkyl; W¹ isselected among H, COW⁶, C0₂W⁶ and SO₂W⁶; W² is selected among OH, NH₂,OW⁶ and NR⁴R⁵; W³ is selected among H and W⁶; W⁴ is selected among H andW⁶; W⁵ is selected among H, OH, and OMe; W⁶ is selected among alkyl,benzyl, aryl and heteroaryl; W⁷ is selected among H, F, Cl, NO₂ and CN;a is selected among 2, 3, 4 and 5; b is selected among 1, 2, 3 and 4; cis selected among 1 and 2; d is selected among 1 and 2; e is selectedamong 1, 2 and 3; f and g are independently selected among 0, 1, 2 and3, such that the sum of f and g is selected among 1, 2 and 3; h isselected among 1 and 2; m is selected among 2, 3, 4, 5, 6 and 7; n isselected among 2, 3 and 4; p is selected among 3 and 4; and q isselected among 3, 4, 5 and
 6. 2. A compound according to claim 1,subject to at least one of the provisos that: when Q=CN; Z=O; X andY═CH₂; R²═H; and R¹ and R³ together are (CH₂)_(p), wherein p=3, then Rshould not be selected among (CH₂)₂CONR⁷R⁸, (CH₂)₃CONR⁷R⁸, CH₂CH(CH₃)CH₂CONR⁷R⁸, and aryl substituted with CONR⁷R⁸; wherein R⁷ and R⁸together form an optionally substituted 4-, 5- or 6-membered C-ring;when Q=CN; Z=O; X and Y═CH₂; R²═H; R¹=isobutyl and R³═H, then R and C=Ztogether should not be selected among the L-alpha-amino acids alanineand arginine; when Q=CN; Z=O; X and Y═CH₂; R²═H; and R¹=—(CH₂)_(a)NHW¹where a=3 or 4 and W¹=(CO)CH₃ or (CO)OCH₂Ph, R³═H, then R should not beselected among methyl and phenyl; when Q=B(OH)₂; Z=O; X and Y═CH₂; R²═H;and R¹=—(CH₂)_(a)NHW¹ where a=4 and W¹=(CO)CH₃, R³═H, then R should notbe methyl; when Q=CHO; Z=O; X and Y═CH₂; R²═H; and R═(CH₂)₃Ph and R³═H,then R¹ should not be selected among (C₁-C₆) alkyl and phenyl(C₁)alkyl;when Q=CHO; Z=O; X and Y═CH2; R²═H and R³ together with R¹ are—(CH₂)_(p)—, wherein p=3, then R should not be a phenyl(C₁-C₄)alkyl;when Q=CHO; Z=O; X and Y═CH₂; R²═H; and R¹=benzyl and R³═H, then Rshould not be 3-(PhO)Ph; when Q=CHO; Z=O; X═S and Y═CH₂; R²═H; andR¹=iBu and R³═H, or when R³ together with R¹ are —(CH₂)_(p)—, where p=3,then R should not be (CH₂)₃-Phenyl; when Q=CHO; Z=O; X and Y═CH₂; R³together with R¹ are —(CH₂)_(p)—, where p=3, then R should not be(CH₂)₃Ph; when Q=CHO or C(═O)CH₂OH; Z=O; X and Y═CH₂; R²═H; and R¹ andR³ together are (CH₂)_(p), wherein p=3, then R should not be selectedamong aryl substituted with CONR⁷R⁸; wherein R⁷ and R⁸ together form anoptionally substituted 5-membered C-ring; and when Q=H; Z=O; X═S andY═CH₂; R³ together with R¹ are —(CH₂)_(p)—, where p=3, then R should notbe CH₂CHR⁹CH₂Aryl, wherein R⁹ is (C₁-C₄) alkyl.
 3. A compound accordingto claim 1, subject to at least one of the provisos that: when Q=CN;Z=O; X and Y═CH₂; R²═H; and R³═H, then R and C=Z together should not beselected among the natural L-alpha-amino acids; when Q=B(OH)₂; Z=O; Xand Y═CH₂; R²═H; and R³═H, then R and C=Z together should not beselected among the natural L-alpha-amino acids; and when Q=CHO; Z=O; Xand Y═CH₂; R²═H; and R¹=benzyl, iPr and iBu and R³═H, or when R³together with R¹ are —(CH₂)_(p)—, where p=3, then R should not be(CH₂)₃OAryl.
 4. A compound according to claim 1, subject to at least oneof the provisos that: R and C=Z together should not be selected amongthe natural L-alpha-amino acids; R should not be selected among (CH₂)₃Phand CH₂CHR⁹CH₂Aryl; and R should not be selected among (CH₂)₂CONR⁷R⁸,(CH₂)₃CONR⁷R⁸, CH₂CH(CH₃) CH₂CONR⁷R⁸, and aryl substituted with CONR⁷R⁸;wherein R7 and R8 together form an optionally substituted 4-, 5- or6-membered C-ring.
 5. A compound according to claim 2, subject to all ofthe provisos of claim
 2. 6. A compound according to claim 1, wherein R²is H.
 7. A compound according to claim 1, wherein R¹ is not H, and thestereogenic center between R¹ and R² has an S-configuration.
 8. Acompound according to claim 1, wherein X is CH₂.
 9. A compound accordingto claim 1, wherein Y is CH₂.
 10. A compound according to claim 1,wherein Z is oxygen.
 11. A compound according to claim 1, wherein R³ isH or alkyl.
 12. A compound according to claim 1, wherein R¹ is H, alkyl,aryl, or aryl(C₁-C₄) alkyl.
 13. A compound according to claim 1 whereinR¹ and R³ together are —(CH₂)_(p)—, wherein p is 3 or
 4. 14. A compoundaccording to claim 1, wherein R¹ and R³ together form a group accordingto the general formula 4 which corresponds to general formula 3 whereinf is 0, g is 1 and h is 2


15. A compound according to claim 1, wherein Q is CN.
 16. A compoundaccording to claim 15, wherein Y is CH₂, and X is selected among S, CH₂,CF₂, CH₂CH₂ and CHF.
 17. A compound according to claim 15, wherein X andY are selected among —CH═CH— and a covalent bond.
 18. A compoundaccording to claim 1, wherein Q is B(OH)₂.
 19. A compound according toclaim 1, wherein Q is C(═O)X¹.
 20. A compound according to claim 19,wherein X¹ is selected among H, alkyl, fluoroalkyl, aryl, aryl(C₁-C₄)alkyl, heteroaryl, and heteroaryl (C₁-C₄)alkyl.
 21. A compound accordingclaim 19, wherein X¹ is selected from CH₂NR⁴R⁵; wherein R⁴ and R⁵ areindependently selected from H, alkyl, alkenyl, aryl, heteroaryl, aryl(C₁-C₄) alkyl and heteroaryl (C₁-C₄) alkyl; or R⁴ and R⁵ together are—(CH₂)_(m)—.
 22. A compound according to claim 19, wherein X¹ isselected from CH₂OR⁶, wherein R⁶ is selected among H, alkyl, alkenyl,aryl, heteroaryl, aryl (C₁-C₄) alkyl, and heteroaryl (C₁-C₄) alkyl. 23.A compound according to claim 1, wherein Q is H.
 24. A compoundaccording to claim 23, wherein X is selected among CH₂, S, CF₂, CHF. 25.A compound, according to claim 1, selected among:(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(4-Methoxybenzoylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Pivaloylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-1-(3-Methoxybenzoyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-1-(Isopropylcarbamoyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3,3-dimethylbutanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-1-(3-Chlorobenzoyl)-pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(3-Methoxybenzoylamino)-4-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Phenylethylthiocarbamoylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-1-(Propylthiocarbamoyl)pyrrolidine-2-carbonyl)pyrrolidine-2-carbonitrile;(2S)-1-(2-(N-(2-Methoxybenzoyl)-N-(2-methylpropyl)amino)acetyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-5-amino-pentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-6-amino-hexanoyl)pyrrolidine-2-carbonitrile;(4R)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylpentanoyl)thiazolidine-4-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylbutanoyl)-4,4-difluoropyrrolidine-2-carbonitrile;(2S)-1-((2S)-1-(Ethylcarbamoyl)pyrrolidine-2-carbonyl)-4,4-difluoropyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoyl)-3,4-dehydropyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoyl)piperidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoyl)azetidine-2-carbonitrile;(4R)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylpentanoyl)thiazolidine-4-carbonitrile-S-oxide;(4R)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylpentanoyl)thiazolidine-4-carbonitrile-S,S-dioxide;1-((2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoyl)pyrrolidine;1-((2S)-2-(2-Methoxybenzoylamino)-3-methylpentanoyl)-3,3-difluoropyrrolidide;1-(2S)-1-(3-Methoxybenzoyl)pyrrolidine-2-carbonyl)-3-thiazolidide;1-((2S)-1-(Isopropylcarbamoyl)pyrrolidine-2-carbonyl)pyrrolidide;(2R)-1-((2S)-2-(2-Methoxybenzoylamino)-3-methylbutanoyl)pyrrolidine-2-boronicacid;(2R)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylbutanoyl)pyrrolidine-2-boronicacid;(2S)-2-Formyl-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide;(2S)-2-Acetyl-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide;(2S)-2-Propionyl-1-((2S)-2-(2-methoxybenzoylamino)-3-methylpentanoyl)pyrrolidide;(2S)-1-(2-(1-Napthoylamino)acetyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(4-Methylbenzoyl)octahydroindole-2-carbonyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(4-Methoxybenzoylamino)-2-cyclohexylacetyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-1-Benzoylpiperidine-2-carbonyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(3-Methoxybenzoylamino)-3-methylbutanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Pivaloylamino)-3-phenylpropanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(N-Cyclohexanoyl-N-methylamino)-3-phenylpropanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3-(methyloxycarbonyl)propanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(4-Chlorobenzoylamino)-4-(benzyloxycarbonyl)butanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(4-Methoxybenzoylamino)-5-(benzyloxycarbonylamino)pentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(3-Methoxybenzoylamino)-6-(benzyloxycarbonylamino)hexanoyl)pyrrolidine-220 carbonitrile;(2S)-1-((2S)-2-(Benzoylamino)-3-benzyloxypropanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Cyclohexanoylamino)-2-phenylacetyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-4-(benzyloxycarbonylamino)butanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-3-(benzyloxycarbonylamino)propanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(N-Cyclohexanoyl-N-methylamino)-propanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(2-Methoxybenzoylamino)-5-N-(acetylamino)-3,3-dimethyl-4-thiopentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(N-(2-Methoxybenzoyl)-N-methylamino)-3-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-(2-(N-Benzyl-N-(2-methoxybenzoyl)amino)acetyl)pyrrolidine-2-carbonitrile;(2S)-1-(2-(2-Methoxybenzoylamino)-2-methylpropanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylbutanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Isopropylcarbamoylamino)propanoyl)-pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Ethylcarbamoyl)octahydroindole-2-carbonyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(N-Ethylcarbamoyl-N-methylamino)-4-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Benzylcarbamoylamino)-3,3-dimethylbutanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Isopropylcarbamoylamino)-3-phenylpropanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Cyclohexylcarbamoylamino)-4-methylpentanoyl)pyrrolidine-2-carbonitrile;(2S)-1-((2S)-2-(Ethylcarbamoylamino)-3-methylpentanoyl)-3,4-dehydropyrrolidine-2-carbonitrile;(2S)-2-Formyl-1-((2S)-2-(2-methoxybenzoylamino)-3-methylbutanoyl)pyrrolidine;(2S)-2-Formyl-1-((2S)-1-(3-methoxybenzoyl)pyrrolidine-2-carbonyl)pyrrolidine;(2S)-2-Formyl-1-((2S)-1-(ethylcarbamoyl)octahydroindole-2-carbonyl)pyrrolidine;(2S)-2Formyl-1-((2S)-2-(2-methoxybenzoyl)-octahydroindole-2-carbonyl)pyrrolidine;and(2S)-2-Formyl-1-((2S)-2-(2-methoxybenzoylamino)-3-phenylpropanoyl)pyrrolidine.26. (canceled)
 27. A pharmaceutical composition comprising a compoundaccording to claim
 1. 28. The pharmaceutical composition according toclaim 27, formulated for oral administration, preferably as a tablet, acapsule or a sachet. 29-38. (canceled)
 39. A method of treatment ofcancer or liver cirrhosis, comprising the administration to a person inneed of such treatment of an effective amount of a compound according toclaim
 1. 40. A method of treatment of conditions in which tissue andmatrix remodelling occurs, comprising the administration to a person inneed of such treatment of an effective amount of a compound according toclaim
 1. 41. A method of treatment according to claim 40, of a conditionselected among malignant and benign tumours, ectopic tissue growth,wound healing, and organ fibrosis and cirrhosis.
 42. A method for theinhibition of metastasis, comprising the administration to a person inneed of such treatment of an effective amount of a compound according toclaim
 1. 43. A method of treatment of blood cell disorders, preferablyanemia and chemotherapy-induced neutropenia, comprising theadministration to a person in need of such treatment of an effectiveamount of a compound according to claim
 1. 44. A compound according toclaim 3, subject to all of the provisos of claim
 3. 45. A compoundaccording to claim 4, subject to all of the provisos of claim 4.